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Genomics in Gynecological Cancer: Future Perspective

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Precision Medicine in Gynecology and Obstetrics

Part of the book series: Comprehensive Gynecology and Obstetrics ((CGO))

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Abstract

All cancers arise as a result of dynamic changes in the cancer genome. Cancer cells show diverse biological capabilities that are conferred by numerous genetic and epigenetic changes. Over the past years, comprehensive genomic studies using next-generation sequencing technology have resulted in an increasing wealth of the understanding of molecular mechanisms with respect to the genomic features of gynecological malignancies, including ovarian, endometrial, and cervical cancers. These studies can be exploited to develop and improve cancer classification, new diagnostic methods, and novel therapeutic strategies.

In this chapter, we review the principles of our current understanding of cancer genomes in gynecological malignancies, particularly ovarian, endometrial, and cervical cancers. Furthermore, a vision for the future of genomics in gynecological cancer has been discussed. We hope that cancer genomic research will ultimately guide clinical decision-making in association with the development of novel therapeutic strategies and biomarker-based clinical trials, affecting the clinical outcome of cancer patients.

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References

  1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  CAS  PubMed  Google Scholar 

  2. Chin L, Gray JW. Translating insights from the cancer genome into clinical practice. Nature. 2008;452:553–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458:719–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  5. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Jr., Kinzler KW. Cancer genome landscapes. Science 2013;339:1546-1558.

    Google Scholar 

  6. Petrillo M, Nero C, Amadio G, Gallo D, Fagotti A, Scambia G. Targeting the hallmarks of ovarian cancer: the big picture. Gynecol Oncol. 2016;142(1):176–83.

    Article  CAS  PubMed  Google Scholar 

  7. Chin L, Andersen JN, Futreal PA. Cancer genomics: from discovery science to personalized medicine. Nat Med. 2011;17:297–303.

    Article  CAS  PubMed  Google Scholar 

  8. Tomczak K, Czerwinska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol (Pozn). 2015;19(1A):A68–77.

    Google Scholar 

  9. Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013;45:1113–20.

    Article  Google Scholar 

  10. Liu J, Westin SN. Rational selection of biomarker driven therapies for gynecologic cancers: the more we know, the more we know we don't know. Gynecol Oncol. 2016;141:65–71.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bast RC, Jr., Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9:415-428.

    Google Scholar 

  12. Katabuchi H, Okamura H. Cell biology of human ovarian surface epithelial cells and ovarian carcinogenesis. Med Electron Microsc. 2003;36:74–86.

    Article  PubMed  Google Scholar 

  13. Okamura H, Katabuchi H. Pathophysiological dynamics of human ovarian surface epithelial cells in epithelial ovarian carcinogenesis. Int Rev Cytol. 2005;242:1–54.

    Article  CAS  PubMed  Google Scholar 

  14. Yap TA, Carden CP, Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 2009;9:167–81.

    Article  CAS  PubMed  Google Scholar 

  15. Tjhay F, Motohara T, Tayama S, Narantuya D, Fujimoto K, Guo J, et al. CD44 variant 6 is correlated with peritoneal dissemination and poor prognosis in patients with advanced epithelial ovarian cancer. Cancer Sci. 2015;106:1421–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kurman RJ, Shih Ie M. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. Hum Pathol. 2011;42:918–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 2012;460:237–49.

    Article  PubMed  Google Scholar 

  18. Shih Ie M, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164:1511–8.

    Article  PubMed  Google Scholar 

  19. Kurman RJ, Shih Ie M. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol. 2008;27:151–60.

    PubMed  PubMed Central  Google Scholar 

  20. Singer G, Kurman RJ, Chang HW, Cho SK, Shih Ie M. Diverse tumorigenic pathways in ovarian serous carcinoma. Am J Pathol. 2002;160:1223–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Senturk E, Cohen S, Dottino PR, Martignetti JA. A critical re-appraisal of BRCA1 methylation studies in ovarian cancer. Gynecol Oncol. 2010;119:376–83.

    Article  CAS  PubMed  Google Scholar 

  22. Liu J, Matulonis UA. New strategies in ovarian cancer: translating the molecular complexity of ovarian cancer into treatment advances. Clin Cancer Res. 2014;20:5150–6.

    Article  CAS  PubMed  Google Scholar 

  23. Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.

    Article  Google Scholar 

  24. Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, et al. Whole-genome characterization of chemoresistant ovarian cancer. Nature. 2015;521:489–94.

    Article  CAS  PubMed  Google Scholar 

  25. Konecny GE, Wang C, Hamidi H, Winterhoff B, Kalli KR, Dering J, et al. Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer. J Natl Cancer Inst. 2014;106

    Google Scholar 

  26. Winterhoff B, Hamidi H, Wang C, Kalli KR, Fridley BL, Dering J, et al. Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures. Gynecol Oncol. 2016;141:95–100.

    Article  CAS  PubMed  Google Scholar 

  27. Bolton KL, Chenevix-Trench G, Goh C, Sadetzki S, Ramus SJ, Karlan BY, et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA. 2012;307:382–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  29. Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Wárlám-Rodenhuis CC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC study group. Post operative radiation therapy in endometrial carcinoma. Lancet. 2000;355:1404–11.

    Article  CAS  PubMed  Google Scholar 

  30. Rauh-Hain JA, Del Carmen MG. Treatment for advanced and recurrent endometrial carcinoma: combined modalities. Oncologist. 2010;15:852–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Group SGOCPECW, Burke WM, Orr J, Leitao M, Salom E, Gehrig P, et al. Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol. 2014;134:393–402.

    Article  Google Scholar 

  32. Creasman WT, Kohler MF, Odicino F, Maisonneuve P, Boyle P. Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium. Gynecol Oncol. 2004;95:593–6.

    Article  PubMed  Google Scholar 

  33. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15:10–7.

    Article  CAS  PubMed  Google Scholar 

  34. Barlin JN, Zhou Q, St Clair CM, Iasonos A, Soslow RA, Alektiar KM, et al. Classification and regression tree (CART) analysis of endometrial carcinoma: seeing the forest for the trees. Gynecol Oncol. 2013;130:452–6.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hecht JL, Mutter GL. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol. 2006;24:4783–91.

    Article  CAS  PubMed  Google Scholar 

  36. Murali R, Soslow RA, Weigelt B. Classification of endometrial carcinoma: more than two types. Lancet Oncol. 2014;15:e268–78.

    Article  PubMed  Google Scholar 

  37. Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch. 2004;444:213–23.

    Article  CAS  PubMed  Google Scholar 

  38. Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 1997;57:3935–40.

    CAS  PubMed  Google Scholar 

  39. Katabuchi H, van Rees B, Lambers AR, Ronnett BM, Blazes MS, Leach FS, et al. Mutations in DNA mismatch repair genes are not responsible for microsatellite instability in most sporadic endometrial carcinomas. Cancer Res. 1995;55:5556–60.

    CAS  PubMed  Google Scholar 

  40. Cancer Genome Atlas Research N, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67-73.

    Google Scholar 

  41. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342–50.

    Article  CAS  PubMed  Google Scholar 

  42. Moody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer. 2010;10:550–60.

    Article  CAS  PubMed  Google Scholar 

  43. Spriggs AI, Boddington MM. Progression and regression of cervical lesions. Review of smears from women followed without initial biopsy or treatment. J Clin Pathol. 1980;33:517–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Christopherson WM, Nealon N, Gray LA, Sr. Noninvasive precursor lesions of adenocarcinoma and mixed adenosquamous carcinoma of the cervix uteri. Cancer. 1979;44:975–83.

    Google Scholar 

  45. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, et al. A review of human carcinogens-part B: biological agents. Lancet Oncol. 2009;10:321–2.

    Article  PubMed  Google Scholar 

  46. Steenbergen RD, Snijders PJ, Heideman DA, Meijer CJ. Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions. Nat Rev Cancer. 2014;14:395–405.

    Article  CAS  PubMed  Google Scholar 

  47. Tewari KS, Monk BJ. New strategies in advanced cervical cancer: from angiogenesis blockade to immunotherapy. Clin Cancer Res. 2014;20:5349–58.

    Article  CAS  PubMed  Google Scholar 

  48. Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, et al. Landscape of genomic alterations in cervical carcinomas. Nature. 2014;506:371–5.

    Article  CAS  PubMed  Google Scholar 

  49. Wright AA, Howitt BE, Myers AP, Dahlberg SE, Palescandolo E, Van Hummelen P, et al. Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix. Cancer. 2013;119:3776–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Annunziata C, Buonaguro L, Buonaguro FM, Tornesello ML. Characterization of the human papillomavirus (HPV) integration sites into genital cancers. Pathol Oncol Res. 2012;18:803–8.

    Article  CAS  PubMed  Google Scholar 

  51. Hu Z, Zhu D, Wang W, Li W, Jia W, Zeng X, et al. Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism. Nat Genet. 2015;47:158–63.

    Article  CAS  PubMed  Google Scholar 

  52. Liu CY, Li F, Zeng Y, Tang MZ, Huang Y, Li JT, et al. Infection and integration of high-risk human papillomavirus in HPV-associated cancer cells. Med Oncol. 2015;32:109.

    Article  PubMed  Google Scholar 

  53. Wong AH, Deng CX. Precision medicine for personalized cancer therapy. Int J Biol Sci. 2015;11:1410–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Aronson SJ, Rehm HL. Building the foundation for genomics in precision medicine. Nature. 2015;526:336–42.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto-City, Kumamoto, 860-8556, Japan

    Takeshi Motohara M.D., Ph.D. & Hidetaka Katabuchi M.D., Ph.D.

Authors
  1. Takeshi Motohara M.D., Ph.D.
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  2. Hidetaka Katabuchi M.D., Ph.D.
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Correspondence to Hidetaka Katabuchi M.D., Ph.D. .

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Editors and Affiliations

  1. National Kyoto Medical Center, Kyoto, Japan

    Ikuo Konishi

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Motohara, T., Katabuchi, H. (2017). Genomics in Gynecological Cancer: Future Perspective. In: Konishi, I. (eds) Precision Medicine in Gynecology and Obstetrics. Comprehensive Gynecology and Obstetrics. Springer, Singapore. https://doi.org/10.1007/978-981-10-2489-4_2

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  • DOI: https://doi.org/10.1007/978-981-10-2489-4_2

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