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Genomic Landscape of Ovarian Cancer

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Abstract

Epithelial ovarian cancer (EOC) remains one of the most challenging areas of cancer research as it is a highly heterogeneous disease from both molecular and etiological points of view. Furthermore, EOC is the fifth leading cause of cancer-related deaths among women, and the leading cause of death from gynecological cancer. Early detection is paramount to increase survival, but only 25% of all EOC are found at an early stage; furthermore, tumors that appear similar based on traditional clinical and histopathologic features may respond very differently to therapy. At the biological level, the most relevant need is for a new molecular classification of EOC that would enable identification of targetable pathways and predict outcome of disease; at the clinical level, the open issues are early detection of disease and early identification of patients with drug-resistant cancers so that alternative therapeutic modalities can be offered.

Microarray-based technologies are powerful tools that may potentially help in understanding the relationship between clinical features of cancers and their underlying biological alterations by measuring the simultaneous structural alteration/expression of thousands of genes. The genomic landscape in EOC, herein described, refers to genomic, functional genomic, and epigenomic studies published in the last 10 years. On the basis of this genomic landscape, the following can be affirmed: (i) all approaches have contributed to the identification of tumor subtypes, but none of the proposed genetic signatures has been sufficiently confirmed or validated; (ii) the clinical question of early identification remains unanswered. In fact, even if there are promising data from epigenetic-based analysis of blood samples from EOC patients, their predictive power is still too low for population-based screening; (iii) genomic and methylation analyses have only recently been carried out on a genome-wide level, and accordingly only a limited number of promising prognostic signatures and predictors have emerged; (iv) gene and miRNA expression analyses, based on more mature technologies, have provided a larger number of promising prognostic signatures and predictors.

In the case of early detection, improvement in terms of accuracy and further confirmation of reliability as specific markers in adequately-sized prospective studies are needed; in the case of prognosis and prediction, it is imperative to confirm potential genetic signatures in large, well annotated independent sets of patient samples coming from multicenter randomized phase III clinical trials. The use of these type of sample sets, combined with the introduction of new high throughput technologies and the integration of data raised by different genome-wide approaches, will hopefully enable a global view of the DNA-RNA relationships and ultimately lead to identification of clinically useful biomarkers.

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References

  1. Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR (2011) Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 11(10):719–725. doi: nrc3144[pii]10.1038/nrc3144

    PubMed  CAS  Google Scholar 

  2. Kurman RJ, Shih IeM (2010) The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 34(3):433–443. doi: 10.1097/PAS.0b013e3181cf3d79

    PubMed  Google Scholar 

  3. Shih I-M, Kurman RJ (2004) Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol 164(5):1511–1518. doi: S0002-9440(10)63708-X[pii]

    PubMed  CAS  Google Scholar 

  4. Kurman RJ, Shih I-M (2011) Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm. Hum Pathol 42(7):918–931. doi: S0046-8177(11)00137-7[pii]10.1016/j.humpath.2011.03.003

    PubMed  CAS  Google Scholar 

  5. Singer G, Kurman RJ, Chang HW, Cho SK, Shih I-M (2002) Diverse tumorigenic pathways in ovarian serous carcinoma. Am J Pathol 160(4):1223–1228. doi: S0002-9440(10)62549-7[pii]

    PubMed  CAS  Google Scholar 

  6. Bast RC Jr, Hennessy B, Mills GB (2009) The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer 9(6):415–428. doi: nrc2644[pii]10.1038/nrc2644

    PubMed  CAS  Google Scholar 

  7. Despierre E, Lambrechts D, Neven P, Amant F, Lambrechts S, Vergote I (2010) The molecular genetic basis of ovarian cancer and its roadmap towards a better treatment. Gynecol Oncol 117(2):358–365. doi: S0090-8258(10)00158-7[pii]10.1016/j.ygyno.2010.02.012

    PubMed  CAS  Google Scholar 

  8. Ahmed AA, Etemadmoghadam D, Temple J, Lynch AG, Riad M, Sharma R, Stewart C, Fereday S, Caldas C, Defazio A, Bowtell D, Brenton JD (2010) Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol 221(1):49–56. doi: 10.1002/path.2696

    PubMed  CAS  Google Scholar 

  9. Senturk E, Cohen S, Dottino PR, Martignetti JA (2010) A critical re-appraisal of BRCA1 methylation studies in ovarian cancer. Gynecol Oncol 119(2):376–383. doi: S0090-8258(10)00555-X[pii]10.1016/j.ygyno.2010.07.026

    PubMed  CAS  Google Scholar 

  10. Watson P, Vasen HF, Mecklin JP, Bernstein I, Aarnio M, Jarvinen HJ, Myrhoj T, Sunde L, Wijnen JT, Lynch HT (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123(2):444–449. doi: 10.1002/ijc.23508

    PubMed  CAS  Google Scholar 

  11. Nakayama K, Nakayama N, Jinawath N, Salani R, Kurman RJ, Shih I-M, Wang TL (2007) Amplicon profiles in ovarian serous carcinomas. Int J Cancer 120(12):2613–2617. doi: 10.1002/ijc.22609

    PubMed  CAS  Google Scholar 

  12. Gilks CB, Prat J (2009) Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 40(9):1213–1223. doi: S0046-8177(09)00140-3[pii]10.1016/j.humpath.2009.04.017

    PubMed  CAS  Google Scholar 

  13. Oliva E, Sarrio D, Brachtel EF, Sanchez-Estevez C, Soslow RA, Moreno-Bueno G, Palacios J (2006) High frequency of beta-catenin mutations in borderline endometrioid tumours of the ovary. J Pathol 208(5):708–713. doi: 10.1002/path.1923

    PubMed  CAS  Google Scholar 

  14. Saegusa M, Machida BD, Okayasu I (2001) Possible associations among expression of p14(ARF), p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 accumulation and the balance of apoptosis and cell proliferation in ovarian carcinomas. Cancer 92(5):1177–1189. doi:10.1002/1097-0142(2901)92:5<1177::AID-CNCR1436>3.0.CO;2-5 [pii]

    PubMed  CAS  Google Scholar 

  15. Wu R, Hendrix-Lucas N, Kuick R, Zhai Y, Schwartz DR, Akyol A, Hanash S, Misek DE, Katabuchi H, Williams BO, Fearon ER, Cho KR (2007) Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-catenin and PI3K/Pten signaling pathways. Cancer Cell 11(4):321–333. doi: S1535-6108(07)00062-1[pii]10.1016/j.ccr.2007.02.016

    PubMed  CAS  Google Scholar 

  16. Kuo KT, Mao TL, Jones S, Veras E, Ayhan A, Wang TL, Glas R, Slamon D, Velculescu VE, Kuman RJ, Shih I-M (2009) Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 174(5):1597–1601. doi: S0002-9440(10)61017-6[pii]10.2353/ajpath.2009.081000

    PubMed  CAS  Google Scholar 

  17. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih I-M, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 363(16):1532–1543. doi: 10.1056/NEJMoa1008433

    PubMed  CAS  Google Scholar 

  18. Gemignani ML, Schlaerth AC, Bogomolniy F, Barakat RR, Lin O, Soslow R, Venkatraman E, Boyd J (2003) Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma. Gynecol Oncol 90(2):378–381. doi: S0090825803002646[pii]

    PubMed  CAS  Google Scholar 

  19. McAlpine JN, Wiegand KC, Vang R, Ronnett BM, Adamiak A, Kobel M, Kalloger SE, Swenerton KD, Huntsman DG, Gilks CB, Miller DM (2009) HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy. BMC Cancer 9:433. doi: 1471-2407-9-433[pii]10.1186/1471-2407-9-433

    PubMed  Google Scholar 

  20. Gorringe KL, Ramakrishna M, Williams LH, Sridhar A, Boyle SE, Bearfoot JL, Li J, Anglesio MS, Campbell IG (2009) Are there any more ovarian tumor suppressor genes? A new perspective using ultra high-resolution copy number and loss of heterozygosity analysis. Genes Chromosomes Cancer 48(10):931–942. doi: 10.1002/gcc.20694

    PubMed  CAS  Google Scholar 

  21. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi: caac.20107[pii]10.3322/caac.20107

    PubMed  Google Scholar 

  22. Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U (2006) Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet 95(Suppl 1):S161–S192. doi: doi:S0020-7292(06)60033-7[pii]10.1016/S0020-7292(06)60033-7

    PubMed  Google Scholar 

  23. Clarke-Pearson DL (2009) Clinical practice. Screening for ovarian cancer. N Engl J Med 361(2):170–177. doi: 361/2/170[pii]10.1056/NEJMcp0901926

    PubMed  CAS  Google Scholar 

  24. Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177(3):1053–1064. doi: S0002-9440(10)60160-5[pii]10.2353/ajpath.2010.15

    PubMed  Google Scholar 

  25. Sandercock J, Parmar MK, Torri V, Qian W (2002) First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence. Br J Cancer 87(8):815–824. doi: 10.1038/sj.bjc.6600567

    PubMed  CAS  Google Scholar 

  26. Agarwal R, Kaye SB (2003) Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer 3(7):502–516. doi: 10.1038/nrc1123nrc1123[pii]

    PubMed  CAS  Google Scholar 

  27. Edgar R, Barrett T (2006) NCBI GEO standards and services for microarray data. Nat Biotechnol 24(12):1471–1472. doi: nbt1206-1471[pii]10.1038/nbt1206-1471

    PubMed  CAS  Google Scholar 

  28. Simon R (2005) Roadmap for developing and validating therapeutically relevant genomic classifiers. J Clin Oncol 23(29):7332–7341. doi: JCO.2005.02.8712[pii]10.1200/JCO.2005.02.8712

    PubMed  CAS  Google Scholar 

  29. Zorn KK, Jazaeri AA, Awtrey CS, Gardner GJ, Mok SC, Boyd J, Birrer MJ (2003) Choice of normal ovarian control influences determination of differentially expressed genes in ovarian cancer expression profiling studies. Clin Cancer Res 9(13):4811–4818

    PubMed  CAS  Google Scholar 

  30. Gilks CB, Vanderhyden BC, Zhu S, van de Rijn M, Longacre TA (2005) Distinction between serous tumors of low malignant potential and serous carcinomas based on global mRNA expression profiling. Gynecol Oncol 96(3):684–694. doi: S0090-8258(04)00903-5[pii]10.1016/j.ygyno.2004.11.039

    PubMed  CAS  Google Scholar 

  31. Meiers I, Shanks JH, Bostwick DG (2007) Glutathione S-transferase pi (GSTP1) hypermethylation in prostate cancer: review 2007. Pathology 39(3):299–304. doi: 779274025[pii]10.1080/00313020701329906

    PubMed  CAS  Google Scholar 

  32. Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474(7353):609–615. doi: nature10166[pii]10.1038/nature10166

    Google Scholar 

  33. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258(5083):818–821

    PubMed  CAS  Google Scholar 

  34. Micci F, Haugom L, Ahlquist T, Andersen HK, Abeler VM, Davidson B, Trope CG, Lothe RA, Heim S (2010) Genomic aberrations in borderline ovarian tumors. J Transl Med 8:21. doi: 1479-5876-8-21[pii]10.1186/1479-5876-8-21

    PubMed  Google Scholar 

  35. Giordano TJ, Shedden KA, Schwartz DR, Kuick R, Taylor JM, Lee N, Misek DE, Greenson JK, Kardia SL, Beer DG, Rennert G, Cho KR, Gruber SB, Fearon ER, Hanash S (2001) Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles. Am J Pathol 159(4):1231–1238. doi: S0002-9440(10)62509-6[pii]10.1016/S0002-9440(10)62509-6

    PubMed  CAS  Google Scholar 

  36. Zorn KK, Bonome T, Gangi L, Chandramouli GV, Awtrey CS, Gardner GJ, Barrett JC, Boyd J, Birrer MJ (2005) Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res 11(18):6422–6430. doi: 11/18/6422[pii]10.1158/1078-0432.CCR-05-0508

    PubMed  CAS  Google Scholar 

  37. Konstantinopoulos PA, Spentzos D, Cannistra SA (2008) Gene-expression profiling in epithelial ovarian cancer. Nat Clin Pract Oncol 5(10):577–587. doi: ncponc1178[pii]10.1038/ncponc1178

    PubMed  CAS  Google Scholar 

  38. Chon HS, Lancaster JM (2011) Microarray-based gene expression studies in ovarian cancer. Cancer Control 18(1):8–15

    PubMed  Google Scholar 

  39. Kim JH, Skates SJ, Uede T, Wong KK, Schorge JO, Feltmate CM, Berkowitz RS, Cramer DW, Mok SC (2002) Osteopontin as a potential diagnostic biomarker for ovarian cancer. JAMA 287(13):1671–1679. doi: joc12052[pii]

    PubMed  CAS  Google Scholar 

  40. Kim JH, Herlyn D, Wong KK, Park DC, Schorge JO, Lu KH, Skates SJ, Cramer DW, Berkowitz RS, Mok SC (2003) Identification of epithelial cell adhesion molecule autoantibody in patients with ovarian cancer. Clin Cancer Res 9(13):4782–4791

    PubMed  CAS  Google Scholar 

  41. Huddleston HG, Wong KK, Welch WR, Berkowitz RS, Mok SC (2005) Clinical applications of microarray technology: creatine kinase B is an up-regulated gene in epithelial ovarian cancer and shows promise as a serum marker. Gynecol Oncol 96(1):77–83. doi: S0090-8258(04)00648-1[pii]10.1016/j.ygyno.2004.08.047

    PubMed  CAS  Google Scholar 

  42. Shvartsman HS, Lu KH, Lee J, Lillie J, Deavers MT, Clifford S, Wolf JK, Mills GB, Bast RC Jr, Gershenson DM, Schmandt R (2003) Overexpression of kallikrein 10 in epithelial ovarian carcinomas. Gynecol Oncol 90(1):44–50. doi: S0090825803002579[pii]

    PubMed  CAS  Google Scholar 

  43. Barton CA, Hacker NF, Clark SJ, O’Brien PM (2008) DNA methylation changes in ovarian cancer: implications for early diagnosis, prognosis and treatment. Gynecol Oncol 109(1):129–139. doi: S0090-8258(07)00981-X[pii]10.1016/j.ygyno.2007.12.017

    PubMed  CAS  Google Scholar 

  44. Makarla PB, Saboorian MH, Ashfaq R, Toyooka KO, Toyooka S, Minna JD, Gazdar AF, Schorge JO (2005) Promoter hypermethylation profile of ovarian epithelial neoplasms. Clin Cancer Res 11(15):5365–5369. doi: 11/15/5365[pii]10.1158/1078-0432.CCR-04-2455

    PubMed  CAS  Google Scholar 

  45. Su HY, Lai HC, Lin YW, Chou YC, Liu CY, Yu MH (2009) An epigenetic marker panel for screening and prognostic prediction of ovarian cancer. Int J Cancer 124(2):387–393. doi: 10.1002/ijc.23957

    PubMed  CAS  Google Scholar 

  46. Montavon C, Gloss BS, Warton K, Barton CA, Statham AL, Scurry JP, Tabor B, Nguyen TV, Qu W, Samimi G, Hacker NF, Sutherland RL, Clark SJ, O’Brien PM (2011) Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer. Gynecol Oncol. doi: S0090-8258(11)00944-9[pii]10.1016/j.ygyno.2011.11.026

    Google Scholar 

  47. de Ibanez de Caceres I, Battagli C, Esteller M, Herman JG, Dulaimi E, Edelson MI, Bergman C, Ehya H, Eisenberg BL, Cairns P (2004) Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients. Cancer Res 64(18):6476–6481. doi: 10.1158/0008-5472.CAN-04-152964/18/6476[pii]

    PubMed  Google Scholar 

  48. Hickey KP, Boyle KP, Jepps HM, Andrew AC, Buxton EJ, Burns PA (1999) Molecular detection of tumour DNA in serum and peritoneal fluid from ovarian cancer patients. Br J Cancer 80(11):1803–1808. doi: 10.1038/sj.bjc.6690601

    PubMed  CAS  Google Scholar 

  49. Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Gayther SA, Apostolidou S, Jones A, Lechner M, Beck S, Jacobs IJ, Widschwendter M (2009) An epigenetic signature in peripheral blood predicts active ovarian cancer. PLoS One 4(12):e8274. doi: 10.1371/journal.pone.0008274

    PubMed  Google Scholar 

  50. Campan M, Moffitt M, Houshdaran S, Shen H, Widschwendter M, Daxenbichler G, Long T, Marth C, Laird-Offringa IA, Press MF, Dubeau L, Siegmund KD, Wu AH, Groshen S, Chandavarkar U, Roman LD, Berchuck A, Pearce CL, Laird PW (2011) Genome-scale screen for DNA methylation-based detection markers for ovarian cancer. PLoS One 6(12):e28141. doi: 10.1371/journal.pone.0028141PONE-D-11-08732[pii]

    PubMed  CAS  Google Scholar 

  51. Ryan BM, Robles AI, Harris CC (2010) Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 10(6):389–402. doi: nrc2867[pii]10.1038/nrc2867

    PubMed  CAS  Google Scholar 

  52. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838. doi: nature03702[pii]10.1038/nature03702

    PubMed  CAS  Google Scholar 

  53. Mezzanzanica D, Bagnoli M, De Cecco L, Valeri B, Canevari S (2010) Role of microRNAs in ovarian cancer pathogenesis and potential clinical implications. Int J Biochem Cell Biol 42(8):1262–1272. doi: S1357-2725(09)00370-7[pii]10.1016/j.biocel.2009.12.017

    PubMed  CAS  Google Scholar 

  54. Hausler SF, Keller A, Chandran PA, Ziegler K, Zipp K, Heuer S, Krockenberger M, Engel JB, Honig A, Scheffler M, Dietl J, Wischhusen J (2010) Whole blood-derived miRNA profiles as potential new tools for ovarian cancer screening. Br J Cancer 103(5):693–700. doi: 6605833[pii]10.1038/sj.bjc.6605833

    PubMed  CAS  Google Scholar 

  55. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE (2009) The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 112(1):55–59. doi: S0090-8258(08)00683-5[pii]10.1016/j.ygyno.2008.08.036

    PubMed  CAS  Google Scholar 

  56. Helland A, Anglesio MS, George J, Cowin PA, Johnstone CN, House CM, Sheppard KE, Etemadmoghadam D, Melnyk N, Rustgi AK, Phillips WA, Johnsen H, Holm R, Kristensen GB, Birrer MJ, Pearson RB, Borresen-Dale AL, Huntsman DG, de Fazio A, Creighton CJ, Smyth GK, Bowtell DD (2011) Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. PLoS One 6(4):e18064. doi: 10.1371/journal.pone.0018064

    PubMed  CAS  Google Scholar 

  57. Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, Johnson DS, Trivett MK, Etemadmoghadam D, Locandro B, Traficante N, Fereday S, Hung JA, Chiew YE, Haviv I, Gertig D, DeFazio A, Bowtell DD (2008) Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res 14(16):5198–5208. doi: 14/16/5198[pii]10.1158/1078-0432.CCR-08-0196

    PubMed  CAS  Google Scholar 

  58. Na YJ, Farley J, Zeh A, del Carmen M, Penson R, Birrer MJ (2009) Ovarian cancer: markers of response. Int J Gynecol Cancer 19(Suppl 2):S21–S29. doi: 10.1111/IGC.0b013e3181c2aeb500009577-200912002-00006[pii]

    PubMed  Google Scholar 

  59. Huan Z, Nakayama K, Nakayama N, Ishibashi M, Yeasmin S, Katagiri A, Purwana IN, Iida K, Maruyama R, Fukumoto M, Miyazaki K (2008) Genetic classification of ovarian carcinoma based on microsatellite analysis: relationship to clinicopathological features and patient survival. Oncol Rep 19(3):775–781

    PubMed  Google Scholar 

  60. Etemadmoghadam D, de Fazio A, Beroukhim R, Mermel C, George J, Getz G, Tothill R, Okamoto A, Raeder MB, Harnett P, Lade S, Akslen LA, Tinker AV, Locandro B, Alsop K, Chiew YE, Traficante N, Fereday S, Johnson D, Fox S, Sellers W, Urashima M, Salvesen HB, Meyerson M, Bowtell D (2009) Integrated genome-wide DNA copy number and expression analysis identifies distinct mechanisms of primary chemoresistance in ovarian carcinomas. Clin Cancer Res 15(4):1417–1427. doi: 1078-0432.CCR-08-1564[pii]10.1158/1078-0432.CCR-08-1564

    PubMed  CAS  Google Scholar 

  61. Cooke SL, Ng CK, Melnyk N, Garcia MJ, Hardcastle T, Temple J, Langdon S, Huntsman D, Brenton JD (2010) Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma. Oncogene 29(35):4905–4913. doi: onc2010245[pii]10.1038/onc.2010.245

    PubMed  CAS  Google Scholar 

  62. Diaz-Padilla I, Amir E, Marsh S, Liu G, Mackay H (2012) Genetic polymorphisms as predictive and prognostic biomarkers in gynecological cancers: a systematic review. Gynecol Oncol 124(2):354–365. doi: S0090-8258(11)00876-6[pii]10.1016/j.ygyno.2011.10.034

    PubMed  CAS  Google Scholar 

  63. Spentzos D, Levine DA, Ramoni MF, Joseph M, Gu X, Boyd J, Libermann TA, Cannistra SA (2004) Gene expression signature with independent prognostic significance in epithelial ovarian cancer. J Clin Oncol 22(23):4700–4710. doi: JCO.2004.04.070[pii]10.1200/JCO.2004.04.070

    PubMed  Google Scholar 

  64. Lancaster JM, Dressman HK, Whitaker RS, Havrilesky L, Gray J, Marks JR, Nevins JR, Berchuck A (2004) Gene expression patterns that characterize advanced stage serous ovarian cancers. J Soc Gynecol Investig 11(1):51–59. doi: S1071557603001710[pii]

    PubMed  CAS  Google Scholar 

  65. Berchuck A, Iversen ES, Lancaster JM, Pittman J, Luo J, Lee P, Murphy S, Dressman HK, Febbo PG, West M, Nevins JR, Marks JR (2005) Patterns of gene expression that characterize long-term survival in advanced stage serous ovarian cancers. Clin Cancer Res 11(10):3686–3696. doi: 11/10/3686[pii]10.1158/1078-0432.CCR-04-2398

    PubMed  CAS  Google Scholar 

  66. Berchuck A, Iversen ES, Luo J, Clarke JP, Horne H, Levine DA, Boyd J, Alonso MA, Secord AA, Bernardini MQ, Barnett JC, Boren T, Murphy SK, Dressman HK, Marks JR, Lancaster JM (2009) Microarray analysis of early stage serous ovarian cancers shows profiles predictive of favorable outcome. Clin Cancer Res 15(7):2448–2455. doi: 1078-0432.CCR-08-2430[pii]10.1158/1078-0432.CCR-08-2430

    PubMed  CAS  Google Scholar 

  67. Mok SC, Bonome T, Vathipadiekal V, Bell A, Johnson ME, Wong KK, Park DC, Hao K, Yip DK, Donninger H, Ozbun L, Samimi G, Brady J, Randonovich M, Pise-Masison CA, Barrett JC, Wong WH, Welch WR, Berkowitz RS, Birrer MJ (2009) A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2. Cancer Cell 16(6):521–532. doi: S1535-6108(09)00386-9[pii]10.1016/j.ccr.2009.10.018

    PubMed  CAS  Google Scholar 

  68. Denkert C, Budczies J, Darb-Esfahani S, Gyorffy B, Sehouli J, Konsgen D, Zeillinger R, Weichert W, Noske A, Buckendahl AC, Muller BM, Dietel M, Lage H (2009) A prognostic gene expression index in ovarian cancer – validation across different independent data sets. J Pathol 218(2):273–280. doi: 10.1002/path.2547

    PubMed  Google Scholar 

  69. Crijns AP, Fehrmann RS, de Jong S, Gerbens F, Meersma GJ, Klip HG, Hollema H, Hofstra RM, te Meerman GJ, de Vries EG, van der Zee AG (2009) Survival-related profile, pathways, and transcription factors in ovarian cancer. PLoS Med 6(2):e24. doi: 08-PLME-RA-1271[pii]10.1371/journal.pmed.1000024

    PubMed  Google Scholar 

  70. Bair E, Tibshirani R (2004) Semi-supervised methods to predict patient survival from gene expression data. PLoS Biol 2(4):E108. doi: 10.1371/journal.pbio.0020108

    PubMed  Google Scholar 

  71. Konstantinopoulos PA, Cannistra SA, Fountzilas H, Culhane A, Pillay K, Rueda B, Cramer D, Seiden M, Birrer M, Coukos G, Zhang L, Quackenbush J, Spentzos D (2011) Integrated analysis of multiple microarray datasets identifies a reproducible survival predictor in ovarian cancer. PLoS One 6(3):e18202. doi: 10.1371/journal.pone.0018202

    PubMed  CAS  Google Scholar 

  72. Spentzos D, Levine DA, Kolia S, Otu H, Boyd J, Libermann TA, Cannistra SA (2005) Unique gene expression profile based on pathologic response in epithelial ovarian cancer. J Clin Oncol 23(31):7911–7918. doi: JCO.2005.02.9363[pii]10.1200/JCO.2005.02.9363

    PubMed  CAS  Google Scholar 

  73. Hartmann LC, Lu KH, Linette GP, Cliby WA, Kalli KR, Gershenson D, Bast RC, Stec J, Iartchouk N, Smith DI, Ross JS, Hoersch S, Shridhar V, Lillie J, Kaufmann SH, Clark EA, Damokosh AI (2005) Gene expression profiles predict early relapse in ovarian cancer after platinum-paclitaxel chemotherapy. Clin Cancer Res 11(6):2149–2155. doi: 11/6/2149[pii]10.1158/1078-0432.CCR-04-1673

    PubMed  CAS  Google Scholar 

  74. Jazaeri AA, Awtrey CS, Chandramouli GV, Chuang YE, Khan J, Sotiriou C, Aprelikova O, Yee CJ, Zorn KK, Birrer MJ, Barrett JC, Boyd J (2005) Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers. Clin Cancer Res 11(17):6300–6310. doi: 11/17/6300[pii]10.1158/1078-0432.CCR-04-2682

    PubMed  CAS  Google Scholar 

  75. Yap TA, Carden CP, Kaye SB (2009) Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer 9(3):167–181. doi: nrc2583[pii]10.1038/nrc2583

    PubMed  CAS  Google Scholar 

  76. Bast RC Jr, Mills GB (2010) Personalizing therapy for ovarian cancer: BRCAness and beyond. J Clin Oncol 28(22):3545–3548. doi: JCO.2010.28.5791[pii]10.1200/JCO.2010.28.5791

    PubMed  CAS  Google Scholar 

  77. Konstantinopoulos PA, Spentzos D, Karlan BY, Taniguchi T, Fountzilas E, Francoeur N, Levine DA, Cannistra SA (2010) Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol 28(22):3555–3561. doi: JCO.2009.27.5719[pii]10.1200/JCO.2009.27.5719

    PubMed  CAS  Google Scholar 

  78. Potti A, Dressman HK, Bild A, Riedel RF, Chan G, Sayer R, Cragun J, Cottrill H, Kelley MJ, Petersen R, Harpole D, Marks J, Berchuck A, Ginsburg GS, Febbo P, Lancaster J, Nevins JR (2006) Genomic signatures to guide the use of chemotherapeutics. Nat Med 12(11):1294–1300. doi: nm1491[pii]10.1038/nm1491

    PubMed  CAS  Google Scholar 

  79. Konstantinopoulos PA, Fountzilas E, Pillay K, Zerbini LF, Libermann TA, Cannistra SA, Spentzos D (2008) Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer. BMC Med Genomics 1:59. doi: 1755-8794-1-59[pii]10.1186/1755-8794-1-59

    PubMed  Google Scholar 

  80. Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A, Olson JA Jr, Marks JR, Dressman HK, West M, Nevins JR (2006) Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 439(7074):353–357. doi: nature04296[pii]10.1038/nature04296

    PubMed  CAS  Google Scholar 

  81. Burks RT, Kessis TD, Cho KR, Hedrick L (1994) Microsatellite instability in endometrial carcinoma. Oncogene 9(4):1163–1166

    PubMed  CAS  Google Scholar 

  82. Gevaert O, De Smet F, Van Gorp T, Pochet N, Engelen K, Amant F, De Moor B, Timmerman D, Vergote I (2008) Expression profiling to predict the clinical behaviour of ovarian cancer fails independent evaluation. BMC Cancer 8:18. doi: 1471-2407-8-18[pii]10.1186/1471-2407-8-18

    PubMed  Google Scholar 

  83. De Smet F, Pochet NL, Engelen K, Van Gorp T, Van Hummelen P, Marchal K, Amant F, Timmerman D, De Moor BL, Vergote IB (2006) Predicting the clinical behavior of ovarian cancer from gene expression profiles. Int J Gynecol Cancer 16(Suppl 1):147–151. doi: IJG321[pii]10.1111/j.1525-1438.2006.00321.x

    PubMed  Google Scholar 

  84. Baldwin RL, Nemeth E, Tran H, Shvartsman H, Cass I, Narod S, Karlan BY (2000) BRCA1 promoter region hypermethylation in ovarian carcinoma: a population-based study. Cancer Res 60(19):5329–5333

    PubMed  CAS  Google Scholar 

  85. Widschwendter M, Jiang G, Woods C, Muller HM, Fiegl H, Goebel G, Marth C, Muller-Holzner E, Zeimet AG, Laird PW, Ehrlich M (2004) DNA hypomethylation and ovarian cancer biology. Cancer Res 64(13):4472–4480. doi: 10.1158/0008-5472.CAN-04-023864/13/4472[pii]

    PubMed  CAS  Google Scholar 

  86. Wiley A, Katsaros D, Chen H, Rigault de la Longrais IA, Beeghly A, Puopolo M, Singal R, Zhang Y, Amoako A, Zelterman D, Yu H (2006) Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential. Cancer 107(2):299–308. doi: 10.1002/cncr.21992

    PubMed  CAS  Google Scholar 

  87. Wei SH, Chen CM, Strathdee G, Harnsomburana J, Shyu CR, Rahmatpanah F, Shi H, Ng SW, Yan PS, Nephew KP, Brown R, Huang TH (2002) Methylation microarray analysis of late-stage ovarian carcinomas distinguishes progression-free survival in patients and identifies candidate epigenetic markers. Clin Cancer Res 8(7):2246–2252

    PubMed  CAS  Google Scholar 

  88. Wei SH, Balch C, Paik HH, Kim YS, Baldwin RL, Liyanarachchi S, Li L, Wang Z, Wan JC, Davuluri RV, Karlan BY, Gifford G, Brown R, Kim S, Huang TH, Nephew KP (2006) Prognostic DNA methylation biomarkers in ovarian cancer. Clin Cancer Res 12(9):2788–2794. doi: 12/9/2788[pii]10.1158/1078-0432.CCR-05-1551

    PubMed  CAS  Google Scholar 

  89. Dai W, Teodoridis JM, Zeller C, Graham J, Hersey J, Flanagan JM, Stronach E, Millan DW, Siddiqui N, Paul J, Brown R (2011) Systematic CpG islands methylation profiling of genes in the wnt pathway in epithelial ovarian cancer identifies biomarkers of progression-free survival. Clin Cancer Res 17(12):4052–4062. doi: 1078-0432.CCR-10-3021[pii]10.1158/1078-0432.CCR-10-3021

    PubMed  CAS  Google Scholar 

  90. Bauerschlag DO, Ammerpohl O, Brautigam K, Schem C, Lin Q, Weigel MT, Hilpert F, Arnold N, Maass N, Meinhold-Heerlein I, Wagner W (2011) Progression-free survival in ovarian cancer is reflected in epigenetic DNA methylation profiles. Oncology 80(1–2):12–20. doi: 000327746[pii]10.1159/000327746

    PubMed  CAS  Google Scholar 

  91. Strathdee G, Vass JK, Oien KA, Siddiqui N, Curto-Garcia J, Brown R (2005) Demethylation of the MCJ gene in stage III/IV epithelial ovarian cancer and response to chemotherapy. Gynecol Oncol 97(3):898–903. doi: S0090-8258(05)00191-5[pii]10.1016/j.ygyno.2005.03.023

    PubMed  CAS  Google Scholar 

  92. Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, Mok SC, D’Andrea AD (2003) Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 9(5):568–574. doi: 10.1038/nm852nm852[pii]

    PubMed  CAS  Google Scholar 

  93. Teodoridis JM, Hall J, Marsh S, Kannall HD, Smyth C, Curto J, Siddiqui N, Gabra H, McLeod HL, Strathdee G, Brown R (2005) CpG island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res 65(19):8961–8967. doi: 65/19/8961[pii]10.1158/0008-5472.CAN-05-1187

    PubMed  CAS  Google Scholar 

  94. Li M, Balch C, Montgomery JS, Jeong M, Chung JH, Yan P, Huang TH, Kim S, Nephew KP (2009) Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer. BMC Med Genomics 2:34. doi: 1755-8794-2-34[pii]10.1186/1755-8794-2-34

    PubMed  Google Scholar 

  95. Gifford G, Paul J, Vasey PA, Kaye SB, Brown R (2004) The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients. Clin Cancer Res 10(13):4420–4426. doi: 10.1158/1078-0432.CCR-03-073210/13/4420[pii]

    PubMed  CAS  Google Scholar 

  96. Chaudhry P, Srinivasan R, Patel FD (2009) Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Cancer Invest 27(8):877–884. doi: 912609607[pii]10.1080/07357900902849699

    PubMed  CAS  Google Scholar 

  97. Kasinski AL, Slack FJ (2011) Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer 11(12):849–864. doi: nrc3166[pii]10.1038/nrc3166

    PubMed  CAS  Google Scholar 

  98. Dahiya N, Morin PJ (2010) MicroRNAs in ovarian carcinomas. Endocr Relat Cancer 17(1):F77–F89. doi: ERC-09-0203[pii]10.1677/ERC-09-0203

    PubMed  CAS  Google Scholar 

  99. Ostrovnaya I, Nanjangud G, Olshen AB (2010) A classification model for distinguishing copy number variants from cancer-related alterations. BMC Bioinformatics 11:297. doi: 1471-2105-11-297[pii]10.1186/1471-2105-11-297

    PubMed  Google Scholar 

  100. Meyniel JP, Cottu PH, Decraene C, Stern MH, Couturier J, Lebigot I, Nicolas A, Weber N, Fourchotte V, Alran S, Rapinat A, Gentien D, Roman-Roman S, Mignot L, Sastre-Garau X (2010) A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer. BMC Cancer 10:222. doi: 1471-2407-10-222[pii]10.1186/1471-2407-10-222

    PubMed  Google Scholar 

  101. Gorringe KL, George J, Anglesio MS, Ramakrishna M, Etemadmoghadam D, Cowin P, Sridhar A, Williams LH, Boyle SE, Yanaihara N, Okamoto A, Urashima M, Smyth GK, Campbell IG, Bowtell DD (2010) Copy number analysis identifies novel interactions between genomic loci in ovarian cancer. PLoS One 5(9). doi: 10.1371/journal.pone.0011408

    Google Scholar 

  102. Bagnoli M, De Cecco L, Granata A, Nicoletti R, Marchesi E, Alberti P, Valeri B, Libra M, Barbareschi M, Raspagliesi F, Mezzanzanica D, Canevari S (2011) Identification of a chrXq27.3 microRNA cluster associated with early relapse in advanced stage ovarian cancer patients. Oncotarge 2(12):1265–1278. doi: 401[pii]

    Google Scholar 

  103. Wrzeszczynski KO, Varadan V, Byrnes J, Lum E, Kamalakaran S, Levine DA, Dimitrova N, Zhang MQ, Lucito R (2011) Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer. PLoS One 6(12):e28503. doi: 10.1371/journal.pone.0028503PONE-D-11-15354[pii]

    PubMed  CAS  Google Scholar 

  104. Nowee ME, Snijders AM, Rockx DA, de Wit RM, Kosma VM, Hamalainen K, Schouten JP, Verheijen RH, van Diest PJ, Albertson DG, Dorsman JC (2007) DNA profiling of primary serous ovarian and fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation-dependent probe amplification. J Pathol 213(1):46–55. doi: 10.1002/path.2217

    PubMed  CAS  Google Scholar 

  105. Yoshihara K, Tajima A, Adachi S, Quan J, Sekine M, Kase H, Yahata T, Inoue I, Tanaka K (2011) Germline copy number variations in BRCA1-associated ovarian cancer patients. Genes Chromosomes Cancer 50(3):167–177. doi: 10.1002/gcc.20841

    PubMed  CAS  Google Scholar 

  106. Schwartz DR, Kardia SL, Shedden KA, Kuick R, Michailidis G, Taylor JM, Misek DE, Wu R, Zhai Y, Darrah DM, Reed H, Ellenson LH, Giordano TJ, Fearon ER, Hanash SM, Cho KR (2002) Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas. Cancer Res 62(16):4722–4729

    PubMed  CAS  Google Scholar 

  107. Schaner ME, Ross DT, Ciaravino G, Sorlie T, Troyanskaya O, Diehn M, Wang YC, Duran GE, Sikic TL, Caldeira S, Skomedal H, Tu IP, Hernandez-Boussard T, Johnson SW, O’Dwyer PJ, Fero MJ, Kristensen GB, Borresen-Dale AL, Hastie T, Tibshirani R, van de Rijn M, Teng NN, Longacre TA, Botstein D, Brown PO, Sikic BI (2003) Gene expression patterns in ovarian carcinomas. Mol Biol Cell 14(11):4376–4386. doi: 10.1091/mbc.E03-05-0279E03-05-0279[pii]

    PubMed  CAS  Google Scholar 

  108. Bonome T, Lee JY, Park DC, Radonovich M, Pise-Masison C, Brady J, Gardner GJ, Hao K, Wong WH, Barrett JC, Lu KH, Sood AK, Gershenson DM, Mok SC, Birrer MJ (2005) Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary. Cancer Res 65(22):10602–10612. doi: 65/22/10602[pii]10.1158/0008-5472.CAN-05-2240

    PubMed  CAS  Google Scholar 

  109. Anglesio MS, Arnold JM, George J, Tinker AV, Tothill R, Waddell N, Simms L, Locandro B, Fereday S, Traficante N, Russell P, Sharma R, Birrer MJ, de Fazio A, Chenevix-Trench G, Bowtell DD (2008) Mutation of ERBB2 provides a novel alternative mechanism for the ubiquitous activation of RAS-MAPK in ovarian serous low malignant potential tumors. Mol Cancer Res 6(11):1678–1690. doi: 6/11/1678[pii]10.1158/1541-7786.MCR-08-0193

    PubMed  CAS  Google Scholar 

  110. Dressman HK, Berchuck A, Chan G, Zhai J, Bild A, Sayer R, Cragun J, Clarke J, Whitaker RS, Li L, Gray J, Marks J, Ginsburg GS, Potti A, West M, Nevins JR, Lancaster JM (2007) An integrated genomic-based approach to individualized treatment of patients with advanced-stage ovarian cancer. J Clin Oncol 25(5):517–525. doi: 25/5/517[pii]10.1200/JCO.2006.06.3743

    PubMed  CAS  Google Scholar 

  111. Schummer M, Ng WV, Bumgarner RE, Nelson PS, Schummer B, Bednarski DW, Hassell L, Baldwin RL, Karlan BY, Hood L (1999) Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene 238(2):375–385. doi: S037811199900342X[pii]

    PubMed  CAS  Google Scholar 

  112. Mok SC, Chao J, Skates S, Wong K, Yiu GK, Muto MG, Berkowitz RS, Cramer DW (2001) Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst 93(19):1458–1464

    PubMed  CAS  Google Scholar 

  113. Meinhold-Heerlein I, Bauerschlag D, Zhou Y, Sapinoso LM, Ching K, Frierson H Jr, Brautigam K, Sehouli J, Stickeler E, Konsgen D, Hilpert F, von Kaisenberg CS, Pfisterer J, Bauknecht T, Jonat W, Arnold N, Hampton GM (2007) An integrated clinical-genomics approach identifies a candidate multi-analyte blood test for serous ovarian carcinoma. Clin Cancer Res 13(2 Pt 1):458–466. doi: 13/2/458[pii]10.1158/1078-0432.CCR-06-0691

    PubMed  CAS  Google Scholar 

  114. Watts GS, Futscher BW, Holtan N, Degeest K, Domann FE, Rose SL (2008) DNA methylation changes in ovarian cancer are cumulative with disease progression and identify tumor stage. BMC Med Genomics 1:47. doi: 1755-8794-1-47[pii]10.1186/1755-8794-1-47

    PubMed  Google Scholar 

  115. Houshdaran S, Hawley S, Palmer C, Campan M, Olsen MN, Ventura AP, Knudsen BS, Drescher CW, Urban ND, Brown PO, Laird PW (2010) DNA methylation profiles of ovarian epithelial carcinoma tumors and cell lines. PLoS One 5(2):e9359. doi: 10.1371/journal.pone.0009359

    PubMed  Google Scholar 

  116. Yoon MS, Suh DS, Choi KU, Sol MY, Shin DH, Park WY, Lee JH, Jeong SM, Kim WG, Shin NR (2010) High-throughput DNA hypermethylation profiling in different ovarian epithelial cancer subtypes using universal bead array. Oncol Rep 24(4):917–925

    PubMed  CAS  Google Scholar 

  117. Gloss BS, Patterson KI, Barton CA, Gonzalez M, Scurry JP, Hacker NF, Sutherland RL, O’Brien PM, Clark SJ (2011) Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers. Cancer Lett. doi: S0304-3835(11)00740-3[pii]10.1016/j.canlet.2011.12.003

    Google Scholar 

  118. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Menard S, Croce CM (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67(18):8699–8707. doi: 67/18/8699[pii]10.1158/0008-5472.CAN-07-1936

    PubMed  CAS  Google Scholar 

  119. Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, Liu CG, Giannakakis A, Alexiou P, Hasegawa K, Johnstone CN, Megraw MS, Adams S, Lassus H, Huang J, Kaur S, Liang S, Sethupathy P, Leminen A, Simossis VA, Sandaltzopoulos R, Naomoto Y, Katsaros D, Gimotty PA, DeMichele A, Huang Q, Butzow R, Rustgi AK, Weber BL, Birrer MJ, Hatzigeorgiou AG, Croce CM, Coukos G (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A 105(19):7004–7009. doi: 0801615105[pii]10.1073/pnas.0801615105

    PubMed  CAS  Google Scholar 

  120. Nam EJ, Yoon H, Kim SW, Kim H, Kim YT, Kim JH, Kim JW, Kim S (2008) MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res 14(9):2690–2695. doi: 14/9/2690[pii]10.1158/1078-0432.CCR-07-1731

    PubMed  CAS  Google Scholar 

  121. Dahiya N, Sherman-Baust CA, Wang TL, Davidson B, Shih I-M, Zhang Y, Wood W 3rd, Becker KG, Morin PJ (2008) MicroRNA expression and identification of putative miRNA targets in ovarian cancer. PLoS One 3(6):e2436. doi: 10.1371/journal.pone.0002436

    PubMed  Google Scholar 

  122. Wyman SK, Parkin RK, Mitchell PS, Fritz BR, O’Briant K, Godwin AK, Urban N, Drescher CW, Knudsen BS, Tewari M (2009) Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One 4(4):e5311. doi: 10.1371/journal.pone.0005311

    PubMed  Google Scholar 

  123. Birrer MJ, Johnson ME, Hao K, Wong KK, Park DC, Bell A, Welch WR, Berkowitz RS, Mok SC (2007) Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas. J Clin Oncol 25(16):2281–2287. doi: 25/16/2281[pii]10.1200/JCO.2006.09.0795

    PubMed  CAS  Google Scholar 

  124. Osterberg L, Levan K, Partheen K, Delle U, Olsson B, Sundfeldt K, Horvath G (2009) Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas. BMC Cancer 9:368. doi: 1471-2407-9-368[pii]10.1186/1471-2407-9-368

    PubMed  Google Scholar 

  125. Osterberg L, Levan K, Partheen K, Delle U, Olsson B, Sundfeldt K, Horvath G (2010) Specific copy number alterations associated with docetaxel/carboplatin response in ovarian carcinomas. Anticancer Res 30(11):4451–4458. doi: 30/11/4451[pii]

    PubMed  Google Scholar 

  126. Marsh S, Paul J, King CR, Gifford G, McLeod HL, Brown R (2007) Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised trial in ovarian cancer. J Clin Oncol 25(29):4528–4535. doi: 25/29/4528[pii]10.1200/JCO.2006.10.4752

    PubMed  CAS  Google Scholar 

  127. Smith S, Su D, Rigault de la Longrais IA, Schwartz P, Puopolo M, Rutherford TJ, Mor G, Yu H, Katsaros D (2007) ERCC1 genotype and phenotype in epithelial ovarian cancer identify patients likely to benefit from paclitaxel treatment in addition to platinum-based therapy. J Clin Oncol 25(33):5172–5179. doi: 25/33/5172[pii]10.1200/JCO.2007.11.8547

    PubMed  CAS  Google Scholar 

  128. Krivak TC, Darcy KM, Tian C, Bookman M, Gallion H, Ambrosone CB, Deloia JA (2011) Single nucleotide polypmorphisms in ERCC1 are associated with disease progression, and survival in patients with advanced stage ovarian and primary peritoneal carcinoma; a gynecologic oncology group study. Gynecol Oncol 122(1):121–126. doi: S0090-8258(11)00235-6[pii]10.1016/j.ygyno.2011.03.027

    PubMed  CAS  Google Scholar 

  129. Galic V, Willner J, Wollan M, Garg R, Garcia R, Goff BA, Gray HJ, Swisher EM (2007) Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas. Genes Chromosomes Cancer 46(3):239–247. doi: 10.1002/gcc.20407

    PubMed  CAS  Google Scholar 

  130. Bartel F, Jung J, Bohnke A, Gradhand E, Zeng K, Thomssen C, Hauptmann S (2008) Both germ line and somatic genetics of the p53 pathway affect ovarian cancer incidence and survival. Clin Cancer Res 14(1):89–96. doi: 14/1/89[pii]10.1158/1078-0432.CCR-07-1192

    PubMed  CAS  Google Scholar 

  131. Paige AJ, Zucknick M, Janczar S, Paul J, Mein CA, Taylor KJ, Stewart M, Gourley C, Richardson S, Perren T, Ganesan TS, Smyth JF, Brown R, Gabra H (2010) WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis. Eur J Cancer 46(4):818–825. doi: S0959-8049(09)00933-2[pii]10.1016/j.ejca.2009.12.021

    PubMed  CAS  Google Scholar 

  132. Marme F, Hielscher T, Hug S, Bondong S, Zeillinger R, Castillo-Tong DC, Sehouli J, Braicu I, Vergote I, Cadron I, Mahner S, Ferschke I, Rom J, Sohn C, Schneeweiss A, Altevogt P (2011) Fibroblast growth factor receptor 4 gene (FGFR4) 388Arg allele predicts prolonged survival and platinum sensitivity in advanced ovarian cancer. Int J Cancer 131(4):E586–E591. doi: 10.1002/ijc.27329

    Google Scholar 

  133. Saldivar JS, Lu KH, Liang D, Gu J, Huang M, Vlastos AT, Follen M, Wu X (2007) Moving toward individualized therapy based on NER polymorphisms that predict platinum sensitivity in ovarian cancer patients. Gynecol Oncol 107(1 Suppl 1):S223–S229. doi: S0090-8258(07)00495-7[pii]10.1016/j.ygyno.2007.07.024

    PubMed  Google Scholar 

  134. Steffensen KD, Waldstrom M, Jeppesen U, Brandslund I, Jakobsen A (2008) Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer. Int J Gynecol Cancer 18(4):702–710. doi: IJG1068[pii]10.1111/j.1525-1438.2007.01068.x

    PubMed  CAS  Google Scholar 

  135. Kim HS, Kim MK, Chung HH, Kim JW, Park NH, Song YS, Kang SB (2009) Genetic polymorphisms affecting clinical outcomes in epithelial ovarian cancer patients treated with taxanes and platinum compounds: a Korean population-based study. Gynecol Oncol 113(2):264–269. doi: S0090-8258(09)00015-8[pii]10.1016/j.ygyno.2009.01.002

    PubMed  CAS  Google Scholar 

  136. Khrunin AV, Moisseev A, Gorbunova V, Limborska S (2010) Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients. Pharmacogenomics J 10(1):54–61. doi: tpj200945[pii]10.1038/tpj.2009.45

    PubMed  CAS  Google Scholar 

  137. Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM, Byth K, Marsh S, McLeod H, Harnett PR, Brown R, DeFazio A, Chenevix-Trench G (2008) ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res 14(17):5594–5601. doi: 14/17/5594[pii]10.1158/1078-0432.CCR-08-0606

    PubMed  CAS  Google Scholar 

  138. Green H, Soderkvist P, Rosenberg P, Mirghani RA, Rymark P, Lundqvist EA, Peterson C (2009) Pharmacogenetic studies of paclitaxel in the treatment of ovarian cancer. Basic Clin Pharmacol Toxicol 104(2):130–137. doi: PTO351[pii]10.1111/j.1742-7843.2008.00351.x

    PubMed  CAS  Google Scholar 

  139. Helleman J, Jansen MP, Span PN, van Staveren IL, Massuger LF, Meijer-van Gelder ME, Sweep FC, Ewing PC, van der Burg ME, Stoter G, Nooter K, Berns EM (2006) Molecular profiling of platinum resistant ovarian cancer. Int J Cancer 118(8):1963–1971. doi: 10.1002/ijc.21599

    PubMed  CAS  Google Scholar 

  140. Jazaeri AA, Yee CJ, Sotiriou C, Brantley KR, Boyd J, Liu ET (2002) Gene expression profiles of BRCA1-linked, BRCA2-linked, and sporadic ovarian cancers. J Natl Cancer Inst 94(13):990–1000

    PubMed  CAS  Google Scholar 

  141. Dixon AR, Ellis IO, Elston CW, Blamey RW (1991) A comparison of the clinical metastatic patterns of invasive lobular and ductal carcinomas of the breast. Br J Cancer 63(4):634–635

    PubMed  CAS  Google Scholar 

  142. Sabatier R, Finetti P, Bonensea J, Jacquemier J, Adelaide J, Lambaudie E, Viens P, Birnbaum D, Bertucci F (2011) A seven-gene prognostic model for platinum-treated ovarian carcinomas. Br J Cancer 105(2):304–311. doi: bjc2011219[pii]10.1038/bjc.2011.219

    PubMed  CAS  Google Scholar 

  143. Partheen K, Levan K, Osterberg L, Claesson I, Fallenius G, Sundfeldt K, Horvath G (2008) Four potential biomarkers as prognostic factors in stage III serous ovarian adenocarcinomas. Int J Cancer 123(9):2130–2137. doi: 10.1002/ijc.23758

    PubMed  CAS  Google Scholar 

  144. Hu X, Macdonald DM, Huettner PC, Feng Z, El Naqa IM, Schwarz JK, Mutch DG, Grigsby PW, Powell SN, Wang X (2009) A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol Oncol 114(3):457–464. doi: S0090-8258(09)00355-2[pii]10.1016/j.ygyno.2009.05.022

    PubMed  CAS  Google Scholar 

  145. Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, Liang S, Leminen A, Deng S, Smith L, Johnstone CN, Chen XM, Liu CG, Huang Q, Katsaros D, Calin GA, Weber BL, Butzow R, Croce CM, Coukos G, Zhang L (2008) MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res 68(24):10307–10314. doi: 68/24/10307[pii]10.1158/0008-5472.CAN-08-1954

    PubMed  CAS  Google Scholar 

  146. Yang H, Kong W, He L, Zhao JJ, O’Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, Cheng JQ (2008) MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 68(2):425–433. doi: 68/2/425[pii]10.1158/0008-5472.CAN-07-2488

    PubMed  CAS  Google Scholar 

  147. Eitan R, Kushnir M, Lithwick-Yanai G, David MB, Hoshen M, Glezerman M, Hod M, Sabah G, Rosenwald S, Levavi H (2009) Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol Oncol 114(2):253–259. doi: S0090-8258(09)00277-7[pii]10.1016/j.ygyno.2009.04.024

    PubMed  CAS  Google Scholar 

  148. Chao A, Lin CY, Lee YS, Tsai CL, Wei PC, Hsueh S, Wu TI, Tsai CN, Wang CJ, Chao AS, Wang TH, Lai CH (2011) Regulation of ovarian cancer progression by microRNA-187 through targeting Disabled homolog-2. Oncogene. doi: onc2011269[pii]10.1038/onc.2011.269

    Google Scholar 

  149. Marchini S, Cavalieri D, Fruscio R, Calura E, Garavaglia D, Nerini IF, Mangioni C, Cattoretti G, Clivio L, Beltrame L, Katsaros D, Scarampi L, Menato G, Perego P, Chiorino G, Buda A, Romualdi C, D’Incalci M (2011) Association between miR-200c and the survival of patients with stage I epithelial ovarian cancer: a retrospective study of two independent tumour tissue collections. Lancet Oncol 12(3):273–285. doi: S1470-2045(11)70012-2[pii]10.1016/S1470-2045(11)70012-2

    PubMed  CAS  Google Scholar 

  150. Shih KK, Qin LX, Tanner EJ, Zhou Q, Bisogna M, Dao F, Olvera N, Viale A, Barakat RR, Levine DA (2011) A microRNA survival signature (MiSS) for advanced ovarian cancer. Gynecol Oncol 121(3):444–450. doi: S0090-8258(11)00069-2[pii]10.1016/j.ygyno.2011.01.025

    PubMed  CAS  Google Scholar 

  151. Kim TH, Kim YK, Kwon Y, Heo JH, Kang H, Kim G, An HJ (2010) Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours. Histopathology 57(5):734–743. doi: 10.1111/j.1365-2559.2010.03686.x

    PubMed  Google Scholar 

  152. Ramakrishna M, Williams LH, Boyle SE, Bearfoot JL, Sridhar A, Speed TP, Gorringe KL, Campbell IG (2010) Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis. PLoS One 5(4):e9983. doi: 10.1371/journal.pone.0009983

    PubMed  Google Scholar 

  153. Ciriello G, Cerami E, Sander C, Schultz N (2011) Mutual exclusivity analysis identifies oncogenic network modules. Genome Res. doi: gr.125567.111[pii]10.1101/gr.125567.111

    Google Scholar 

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Acknowledgements

This study was supported by grants to SC from the Italian Association for Cancer Research (AIRC IG-10302 2010) and the Italian Ministry of Health (P.I.O. RFPS-2006-2-341988.4 and “Progetto Oncologico di Medicina Molecolare: i Tumori Femminili”). We thank Dr. Patrick Moore for editing the manuscript.

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Authors and Affiliations

  1. Unit of Molecular Therapies, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Delia Mezzanzanica, Marina Bagnoli & Patrizia Pinciroli

  2. Functional Genomics Core Facility, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Loris De Cecco

  3. Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Marco A. Pierotti

  4. Unit of Molecular Therapies and Functional Genomics Core Facility, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Silvana Canevari

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  1. Delia Mezzanzanica
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  2. Loris De Cecco
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  3. Marina Bagnoli
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  4. Patrizia Pinciroli
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  5. Marco A. Pierotti
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Correspondence to Delia Mezzanzanica .

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  1. , Integrated Molecular Pathology, National Cancer Research Institute, Largo Rosanna Benzi 10, Genova, 16132, Italy

    Ulrich Pfeffer

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Mezzanzanica, D., De Cecco, L., Bagnoli, M., Pinciroli, P., Pierotti, M.A., Canevari, S. (2013). Genomic Landscape of Ovarian Cancer. In: Pfeffer, U. (eds) Cancer Genomics. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5842-1_10

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