A rare case of low-grade ovarian serous carcinoma with NRAS mutation in a female BRCA1 pathogenic variant carrier


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Abstract

Background: The dualistic theory of ovarian cancer has been currently accepted. Types 1 and 2 tumors are different molecular biological masses and are not components of the same pathway of carcinogenesis. They differ in the morphological pattern, molecular prof ile, clinical course, and approaches to therapy. It is important for clinical practice to establish the true cause of cancer, as this may affect treatment policy in patients. Case report: The paper describes a clinical case of a combination of the mutations characteristic of Types 1 and 2 tumors: the patient has been found to have a combination of a germline mutation in the BRCA1 gene and a somatic mutation in the NRAS gene and the development of the tumor along the molecule cascade that is uncharacteristic for BRCA1 mutation carriers. Conclusion: The identification of the true genetic cause of the development of an ovarian tumor is emphasized to be of great importance, since this affects the treatment strategy.

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About the authors

Tatiana V. Gorodnova

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

PhD, Researcher at the Department of Oncogynecology

Anna P. Sokolenko

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia

PhD, Researcher at the Department of Tumor Biology

Khristina B. Kotiv

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia

Email: kotiv.onc@gmail.com
PhD, Researcher at the Department of Oncogynecology

Alexander O. Ivantsov

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

Email: shurikiv@mail.ru
Dr. Med. Sci., Academic Secretary

Zaur N. Ibragimov

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

Email: zaur-ibragimov@yandex.ru
PhD, Researcher at the Department of Oncogynecology

Igor V. Berlev

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia

Email: i.berliv@gmail.com
Dr. Merd. Sci., Head of the Department of Oncogynecology

Adelia F. Urmancheeva

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia

Email: adaurm@mail.ru
Dr. Med. Sci., Leading Researcher at the Department of Oncogynecology

Evgeny N. Imyanitov

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia; Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia

Email: evgeny@imyanitov.spbru
Dr. Med. Sci., Professor, Corresponding Member of the RAS, Head of the Department of Tumor Biology

References

  1. Vercellini P., Crosignani P., Somigliana E., Vigano P., Buggio L., Bolis G., Fedele L. The “incessant menstruation” hypothesis: a mechanistic ovarian cancer model with implications for prevention. Hum. Reprod. 2011; 26(9): 2262-73. https://dx.doi.org/10.1093/humrep/der211.
  2. Saad A., Hu W., Sood A. Microenvironment and pathogenesis of epithelial ovarian cancer. Horm. Cancer. 2010; 1(6): 277-90. https://dx.doi.org/10.1007/s12672-010-0054-2.
  3. Munksgaard P., Blaakaer J. The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations. Gynecol. Oncol. 2012; 124(1): 164-9. https://dx.doi.org/10.1016/j.ygyno.2011.10.001.
  4. Sadlecki P., Walentowicz-Sadlecka M., Grabiec M. Molecular diagnosis in type I. epithelial ovarian cancer. Ginekol. Pol. 2017; 88(12): 692-7. https://dx.doi.org/10.5603/GP.a2017.0123.
  5. Xing D., Rahmanto Y.S., Zeppernick F., Hannibal C.G., Kjaer S.K., Vang R. et al. Mutation of NRAS is a rare genetic event in ovarian low-grade serous carcinoma. Hum. Pathol. 2017; 68: 87-91. https://dx.doi.org/10.1016/j.humpath.2017.08.021.
  6. Vang R., Shih I., Kurman R. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv. Anat. Pathol. 2009; 16(5): 267-82. https://dx.doi.org/10.1097/ PAP.0b013e3181b4fffa.
  7. Wong K., Tsang Y., Deavers M., Mok S.C., Zu Z., Sun C. et al. BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas. Am. J. Pathol. 2010; 177(4): 1611-7. https://dx.doi.org/10.2353/ajpath.2010.100212.
  8. Ardighieri L., Zeppernick F., Hannibal C., Vang R., Cope L., Junge J. et al. Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants. J. Pathol. 2014; 232(1): 16-22. https://dx.doi.org/10.1002/path.4293.
  9. Heublein S., Grasse K., Hess el H., Burges A., Lenhard M., Engel J. et al. KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants. BMC Cancer. 2013; 13: 483. https://dx.doi.org/10.1186/1471-2407-13-483.
  10. Tsang Y., Deavers M., Sun C., Kwan S.Y., Kuo E., Malpica A. et al. KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma. J. Pathol. 2013; 231(4): 449-56. https://dx.doi.org/10.1002/path.4252.
  11. Hunter S., Anglesio M., Ryland G., Sharma R., Chiew Y.E., Rowley S.M. et al. Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes. Oncotarget. 2015; 6(35): 37663-77. https://dx.doi.org/10.18632/oncotarget.5438.
  12. Alsop K., Fereday S., Meldrum C., deFazio A., Emmanuel C., George J. et al. BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation-Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group. J. Clin. Oncol. 2012; 30(21): 2654-63. https://dx.doi.org/10.1200/JCO.2011.39.8545.
  13. Walker J.L., Powell C.B., Chen L., Carter J., Bae Jump V.L., Parker L.P. et al. Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer. Cancer. 2015; 121(13): 2108-20. https://dx.doi.org/10.1002/ CNCR.29321.
  14. Carlson J., Miron A., Jarboe E., Parast M.M., Hirsch M.S., Lee Y. et al. Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention. J. Clin. Oncol. 2008; 26(25): 4160-5. https://dx.doi.org/10.1200/JCO.2008.16.4814.
  15. Kurman R. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma. Ann. Oncol. 2013; 24(10, Suppl.): 16-21. https://dx.doi.org/10.1093/annonc/mdt463.
  16. Vang R., Shih I., Kurman R. Fallopian tube precursors of ovarian low-and high-grade serous neoplasms. Histopathology. 2013; 62(1): 44-58. https://dx.doi.org/10.1111/his.12046.
  17. Cole A.J., Dwight T., Gill A.J., Dickson K.A., Zhu Y., Clarkson A. et al. Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing. Sci. Rep. 2016; 18(6): 26191. https://dx.doi.org/10.1038/srep26191.
  18. Kindelberger D., Lee Y., Miron A., Hirsch M.S., Feltmate C., Medeiros F. et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am. J. Surg. Pathol. 2007; 31(2): 161-9. https://dx.doi.org/10.1097/01.pas.0000213335.40358.47.
  19. Bowtell D. The genesis and evolution of high-grade serous ovarian cancer. Nat. Rev. Cancer. 2010; 10(11): 803-8. https://dx.doi.org/10.1038/nrc2946.
  20. Norquist B., Garcia R., Allison K., Jokinen C.H., Kernochan L.E., Pizzi C.C. et al. The molecular pathogenesis of hereditary ovarian carcinoma: alterations in the tubal epithelium of women with BRCA1 and BRCA2 mutations. Cancer. 2010; 116(22): 5261-71. https://dx.doi.org/10.1002/cncr.25439.
  21. Werness B., Parvatiyar P., Ramus S., Whittemore A.S., Garlinghouse-Jones K., Oakley-Girvan I. et al. Ovarian carcinoma in situ with germline BRCA1 mutation and loss of heterozygosity at BRCA1 and TP53. J. Natl. Cancer Inst. 2000; 92(13): 1088-91. https://dx.doi.org/10.1093/jnci/92.13.1088.
  22. Gorodnova T.V., Sokolenko A.P., Ivantsov A.O., Iyevleva A.G., Suspitsin E.N., Aleksakhina S.N. et al. High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation. Cancer Lett. 2015; 369(2): 363-7. https://dx.doi.org/10.1016/j.canlet.2015.08.028.
  23. Sokolenko A.P., Savonevich E.L., Ivantsov A.O., Raskin G.A., Kuligina E.S., Gorodnova T.V. et al. Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers. Cancer Lett. 2017; 397: 127-32. https://dx.doi.org/10.1016/j.canlet.2017.03.036.
  24. Берлев И.В., Беляев А.М., Карачун А.М., Городнова Т.В., Доманский А.А., Пелипась Ю.В., Гусейнов К.Д., Ибрагимов З.Н., Соколенко А.П., Яковева М.Г. и др. Циторедуктивные операции с перитонеумэктомией у больных раком яичников: технические аспекты и непосредственные результаты. Вопросы онкологии. 2018; 64(3): 345-52. https://dx.doi.org/10.37469/0507-3758-2018-64-3-345-352.
  25. Жорданиа К.И., Паяниди Ю.Г., Калиничева Е.В. Парадигма этиологии серозного рака яичников. Акушерство и гинекология. 2014; 9: 10-5.

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