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Genomics in Gynaecological Cancer: What the Clinician Needs to Know

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Abstract

The availability and decreasing cost of molecular testing and acceptance of the value of molecular information in clinical care have changed the approach to classification, risk assessment and treatment of cancer. Gynaecological cancers include a diverse array of tumours arising at each site in the female genital tract. Diagnosis and classification are still based on histological appearance supported by immunohistochemistry but refined by the identification of specific genetic abnormalities or molecular subgroups.

In endometrial cancer four prognostically distinct groups of tumours are identified, characterized by the burden of tumour mutation and somatic copy number alterations. Pragmatic classification systems have been developed which can be used in routine practice with techniques which are widely available in diagnostic laboratories. This allows triage for familial cancer screening, and it is anticipated that clinical trials will demonstrate the benefit of personalised treatment strategies. In ovarian cancer, the identification of homologous recombinant deficiencies including germline and somatic pathogenic variants of BRCA1 and BRCA2 genes informs therapeutic decisions. Identification of specific mutations may permit targeted therapy. Some sarcomas have characteristic chromosomal rearrangements and in cervical and vulval cancers distinction is made between HPV associated and HPV independent tumours.

Keywords

  • Molecular pathology
  • Gynaecological cancer
  • WHO classification
  • Homologous recombinant deficiency
  • Mismatch repair proteins

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  • DOI: 10.1007/978-3-030-94110-9_16
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References

  1. WHO Classification of Tumours Editorial Board. Female genital tract, WHO classification of tumours. 5 ed. IARC. 2020.

    Google Scholar 

  2. Singh N, McCluggage WG, Gilks CB. High-grade serous carcinoma of tubo-ovarian origin: recent developments. Histopathology. 2017;71(3):339–56.

    CrossRef  Google Scholar 

  3. Köbel M, Piskorz AM, Lee S, Lui S, LePage C, Marass F, Rosenfeld N, Mes Masson AM, Brenton JD. Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. J Pathol Clin Res. 2016;2(4):247–58.

    CrossRef  Google Scholar 

  4. Kang HJ, Chun SM, Kim KR, Sohn I, Sung CO. Clinical relevance of gain-of-function mutations of p53 in high-grade serous ovarian carcinoma. PLoS One. 2013;13:8.

    Google Scholar 

  5. Pennington KP, Walsh T, Harrell MI, Lee MK, Pennil CC, Rendi MH, Thornton A, Norquist BM, Casadei S, Nord AS, Agnew KJ, Pritchard CC, Scroggins S, Garcia RL, King MC, Swisher EM. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014;20(3):764–75.

    CAS  CrossRef  Google Scholar 

  6. Sundar S, Manchanda R, Gourley C, George A, Wallace A, Balega J, Williams S, Wallis Y, Edmondson R, Nicum S, Frost J, Attygalle A, Fotopoulou C, Bowen R, Bell D, Gajjar K, Ramsay B, Wood NJ, Ghaem-Maghami S, Miles T, Ganesan R. British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for germline and tumor testing for BRCA1/2 variants in ovarian cancer in the United Kingdom. Int J Gynecol Cancer. 2021;31(2):272–8.

    PubMed  Google Scholar 

  7. Hunter SM, Anglesio MS, Ryland GL, Sharma R, Chiew YE, Rowley SM, Doyle MA, Li J, Gilks CB, Moss P, Allan PE, Stephens AN, Huntsman DG, de Fazio A, Bowtell DD, Australian Ovarian Cancer Study Group, Gorringe KL, Campbell IG. Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes. Oncotarget. 2015;6(35):37663–77.

    CrossRef  Google Scholar 

  8. McConechy MK, Ding J, Senz J, Yang W, Melnyk N, Tone AA, Prentice LM, Wiegand KC, McAlpine JN, Shah SP, Lee CH, Goodfellow PJ, Gilks CB, Huntsman DG. Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles. Mod Pathol. 2014;27(1):128–34.

    CAS  CrossRef  Google Scholar 

  9. Khalique S, Naidoo K, Attygalle AD, Kriplani D, Daley F, Lowe A, Campbell J, Jones T, Hubank M, Fenwick K, Matthews N, Rust AG, Lord CJ, Banerjee S, Natrajan R. Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A mutational status in gynaecological cancers. J Pathol Clin Res. 2018;4(3):154–66.

    CAS  CrossRef  Google Scholar 

  10. Cheasley D, Wakefield MJ, Ryland GL, Allan PE, Alsop K, Amarasinghe KC, Ananda S, Anglesio MS, Au-Yeung G, Böhm M, Bowtell DDL, Brand A, Chenevix-Trench G, Christie M, Chiew YE, Churchman M, DeFazio A, Demeo R, Dudley R, Fairweather N, Fedele CG, Fereday S, Fox SB, Gilks CB, Gourley C, Hacker NF, Hadley AM, Hendley J, Ho GY, Hughes S, Hunstman DG, Hunter SM, Jobling TW, Kalli KR, Kaufmann SH, Kennedy CJ, Köbel M, Le Page C, Li J, Lupat R, McNally OM, McAlpine JN, Mes-Masson AM, Mileshkin L, Provencher DM, Pyman J, Rahimi K, Rowley SM, Salazar C, Samimi G, Saunders H, Semple T, Sharma R, Sharpe AJ, Stephens AN, Thio N, Torres MC, Traficante N, Xing Z, Zethoven M, Antill YC, Scott CL, Campbell IG, Gorringe KL. The molecular origin and taxonomy of mucinous ovarian carcinoma. Nat Commun. 2019;10(1):3935.

    CrossRef  Google Scholar 

  11. Karnezis AN, Wang Y, Keul J, Tessier-Cloutier B, Magrill J, Kommoss S, Senz J, Yang W, Proctor L, Schmidt D, Clement PB, Gilks CB, Huntsman DG, Kommoss F. DICER1 and FOXL2 mutation status correlates with clinicopathologic features in ovarian Sertoli-Leydig cell tumors. Am J Surg Pathol. 2019;43(5):628–38.

    CrossRef  Google Scholar 

  12. Witkowski L, Carrot-Zhang J, Albrecht S, Fahiminiya S, Hamel N, Tomiak E, Grynspan D, Saloustros E, Nadaf J, Rivera B, Gilpin C, Castellsagué E, Silva-Smith R, Plourde F, Wu M, Saskin A, Arseneault M, Karabakhtsian RG, Reilly EA, Ueland FR, Margiolaki A, Pavlakis K, Castellino SM, Lamovec J, Mackay HJ, Roth LM, Ulbright TM, Bender TA, Georgoulias V, Longy M, Berchuck A, Tischkowitz M, Nagel I, Siebert R, Stewart CJ, Arseneau J, McCluggage WG, Clarke BA, Riazalhosseini Y, Hasselblatt M, Majewski J, Foulkes WD. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat Genet. 2014;46(5):438–43.

    CAS  CrossRef  Google Scholar 

  13. Zhang X, Yan K, Chen J, Xie X. Using short tandem repeat analysis for choriocarcinoma diagnosis: a case series. Diagn Pathol. 2019;14(1):93. https://doi.org/10.1186/s13000-019-0866-5.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  14. de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D’Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL. PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(3):295–309.

    CrossRef  Google Scholar 

  15. Stelloo E, Jansen AML, Osse EM, Nout RA, Creutzberg CL, Ruano D, Church DN, Morreau H, Smit VTHBM, van Wezel T, Bosse T. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol. 2017;28(1):96–102.

    CAS  CrossRef  Google Scholar 

  16. Hampel H, Pearlman R, de la Chapelle A, Pritchard CC, Zhao W, Jones D, Yilmaz A, Chen W, Frankel WL, Suarez AA, Cosgrove C, Backes F, Copeland L, Fowler J, O’Malley D, Salani R, McElroy JP, Stanich PP, Goodfellow P, Cohn DE. Double somatic mismatch repair gene pathogenic variants as common as Lynch syndrome among endometrial cancer patients. Gynecol Oncol. 2021;160(1):161–8.

    CAS  CrossRef  Google Scholar 

  17. Curti BD, Faries MB. Recent advances in the treatment of melanoma. N Engl J Med. 2021;384(23):2229–40.

    CAS  CrossRef  Google Scholar 

  18. Hou JY, Baptiste C, Hombalegowda RB, Tergas AI, Feldman R, Jones NL, Chatterjee-Paer S, Bus-Kwolfski A, Wright JD, Burke WM. Vulvar and vaginal melanoma: a unique subclass of mucosal melanoma based on a comprehensivemolecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma. Cancer. 2017;123(8):1333–44.

    CAS  CrossRef  Google Scholar 

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Oniscu, A., Attygalle, A., Williams, A. (2022). Genomics in Gynaecological Cancer: What the Clinician Needs to Know. In: Singh, K., Gupta, B. (eds) Gynecological Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-94110-9_16

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  • DOI: https://doi.org/10.1007/978-3-030-94110-9_16

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