A rare case of low-grade ovarian serous carcinoma with NRAS mutation in a female BRCA1 pathogenic variant carrier
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 profile, 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.Gorodnova T.V., Sokolenko A.P., Kotiv Kh.B., Ivantsov A.O., Ibragimov Z.N., Berlev I.V., Urmancheeva A.F., Imyanitov E.N.
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.
Keywords
NRAS mutation
BRCA1 mutation
low-grade serous ovarian carcinoma
high-grade serous ovarian carcinoma
References
- Vercellini P., Crosignani P., Somigliana E., Viganò 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.
- 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.
- 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.
- Sadłecki P., Walentowicz-Sadłecka 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.
- 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.
- 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.
- 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.
- 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.
- Heublein S., Grasse K., Hessel 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. [Berlev I.V., Belyaev A.M., Karachun A.M., Gorodnova T.V., Domansky A.A., Pelipas Yu.V., Huseynov K.D., Ibragimov Z.N., Sokolenko A.P., Yakoveva M.G. et al. Cytoreductive operations with peritoneumectomy in patients with ovarian cancer: technical aspects and immediate results. Issues of oncology. 2018; 64(3): 345-52. (in Russian)]. https://dx.doi.org/10.37469/0507-3758-2018-64-3-345-352.
- Жорданиа К.И., Паяниди Ю.Г., Калиничева Е.В. Парадигма этиологии серозного рака яичников. Акушерство и гинекология. 2014; 9: 10-5. [Zhordania K.I., Payanidi Yu.G., Kalinicheva E.V. The paradigm of the etiology of serous ovarian cancer. Obstetrics and Gynecology. 2014; 9: 10-5. (in Russian)].
Received 27.12.2021
Accepted 02.03.2022
About the Authors
Tatiana V. Gorodnova, PhD, Researcher at the Department of Oncogynecology, N.N. Petrov NMRC of Oncology, Ministry of Health of Russia,197758, Russia, St.-Petersburg, Leningradskaya str., 68, t.gorodnova@mail.ru, https://orcid.org/0000-0003-1719-7498, SPIN-code: 2661-9106, Scopus AuthorID: 36010503000
Anna P. Sokolenko, PhD, Researcher at the Department of Tumor Biology, N.N. Petrov NMRC of Oncology, Ministry of Health of Russia, 197758, Russia, St.-Petersburg, Leningradskaya str., 68; Associate Professor at the Department of General and Molecular Medical Genetics, St.-Petersburg SPMU, Ministry of Health of Russia,
194100, Russia, Saint-Petersburg, Litovskaya str., 2, annasokolenko@mail.ru, https://orcid.org/0000-0001-6304-1609, Scopus AuthorID: 7004209770,
Researcher ID: G-3123-2013
Khristina B. Kotiv, PhD, Researcher at the Department of Oncogynecology, N.N. Petrov NMRC of Oncology, Ministry of Health of Russia,
197758, Russia, St.-Petersburg, Leningradskaya str., 68; Аssistant at the Department of Obstetrics and Gynecology, NWSMU named after I. I. Mechnikov, Ministry of Health
of Russia, 191015, Russia, Saint-Petersburg, Kirochnaya str., 41, kotiv.onc@gmail.com, ORCID 0000-0002-0486-2404, SPIN-code: 3049-8250, Scopus AuthorID: 57193895371
Alexander O. Ivantsov, Dr. Med. Sci., Academic Secretary, N.N. Petrov NMRC of Oncology, Ministry of Health of Russia,
197758, Russia, St.-Petersburg, Leningradskaya str., 68, shurikiv@mail.ru, https://orcid.org/0000-0001-6279-2312, SPIN-код: 8347-0332
Zaur N. Ibragimov, PhD, Researcher at the Department of Oncogynecology, N.N. Petrov NMRC of Oncology, Ministry of Health of Russia,
197758, Russia, St.-Petersburg, Leningradskaya str., 68, zaur-ibragimov@yandex.ru
Igor V. Berlev, Dr. Merd. Sci., Head of the Department of Oncogynecology, N.N. Petrov NMRC of Oncology, Ministry of Health of Russia,
197758, Russia, St.-Petersburg, Leningradskaya str., 68; Head of the Department of Obstetrics and Gynecology, NWSMU named after I. I. Mechnikov, Ministry of Health
of Russia, 191015, Russia, Saint-Petersburg, Kirochnaya str., 41, i.berliv@gmail.com, SPIN-код: 4169-6011, AuthorID: 668976, Scopus AuthorID: 6603322008
Adelia F. Urmancheeva, Dr. Med. Sci., Leading Researcher at the Department of Oncogynecology, N.N. Petrov NMRC of Oncology, Ministry of Health of Russia,
197758, Russia, St.-Petersburg, Leningradskaya str., 68; Head of Curriculum of Oncology, NWSMU named after I. I. Mechnikov, Ministry of Health of Russia,
91015, Russia, Saint-Petersburg, Kirochnaya str., 41, adaurm@mail.ru, https://orcid.org/0000-0003-2835-2983, SPIN-код: 4169-6011
Evgeny N. Imyanitov, Dr. Med. Sci., Professor, Corresponding Member of the RAS, Head of the Department of Tumor Biology, N.N. Petrov NMRC of Oncology,
Ministry of Health of Russia, 197758, Russia, St.-Petersburg, Leningradskaya str., 68; Head of the Department of Tumor Biology, St.-Petersburg SPMU, Ministry of Health of Russia, 194100, Russia, Saint-Petersburg, Litovskaya str., 2, evgeny@imyanitov.spb.ru,
https://orcid.org/0000-0003-4529-7891, SPIN-code: 1909-7323, Scopus AuthorID: 7003644486
Authors' contributions: Gorodnova T.V., Sokolenko A.P., Ivantsov A.O. – development of the concept of the research, fair manuscript version; Kotiv Kh.B., Ibragimov Z.N. – design of the article; manuscript drafting; Berlev I.V., Urmancheeva A.F., Imyanitov E.N. – critical revision with the introduction of valuable intellectual content.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The investigation has been supported by the Russian Science Foundation Grant No. 21-75-30015.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia.
Patients Consent for Publication: The patient provided informed consent for the publication of her data and associated images.
For citation: Gorodnova T.V., Sokolenko A.P., Kotiv Kh.B., Ivantsov A.O.,
Ibragimov Z.N., Berlev I.V., Urmancheeva A.F., Imyanitov E.N. A rare case
of low-grade ovarian serous carcinoma with NRAS mutation
in a female BRCA1 pathogenic variant carrier.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 4: 176-182 (in Russian)
https://dx.doi.org/10.18565/aig.2022.4.176-182
Similar Articles
