BRCA1 and BRCA2 genes mutations in patients with multiple primary tumors

О. В. Палійчук

Abstract


Multiple primary tumors are understudied cancer. Criteria multiplicity of primary tumor: a tumor should be located in different organs, their morphology must be unequal, and each tumor

should provide their own metastases. At the time of appearance there are synchronous and metachronous tumors.

The study to compare the clinical characteristics of multiple primary cancers of the female reproductive system and results of morphological and molecular genetic tumor research was performed.

The complex clinical, morphological and molecular genetic research included 44 patients aged 23–83 years with primary multiple malignant tumors of the female reproductive system, in families whose relatives suffered from cancer of the first and second degree, which corresponds to a cancer family syndrome (Lynch syndrome II). Molecular genetic study included identification of the most common in the Slavic populations BRCA1 and BRCA2 genes mutations – 5382insC and 6174delT respectively.

Study found 5382insC mutations in the BRCA1 gene in patients whose primary tumor was breast cancer, heterogeneity of tumor morphology, degree of differentiation and the clinical course, which was judged on the basis of analysis of cancer recurrence. 5382insC mutations in BRCA1 gene and 6174delT mutations in BRCA2 gene detected in 8 (18.2%) patients, the primary tumor had a different genesis. In most of the cases (6 patients out of 8) of metachronous tumor was ovarian cancer. The presence of mutations in the investigated tumors indicates their role in the development of breast cancer and ovarian cancer. Further investigation need to identify association between different genesis tumors with BRCA1 and BRCA2 gene mutations and investigation of hereditary pathological processes and the possible presence of these mutations in relatives of patients with breast or ovarian cancer.

It is proved the BRCA1/2 genes mutations as a predictive factor of the recurrence cancer risk in proband’s relatives.


Keywords


multiple primary tumors; BRCA1 and the BRCA2 genes; 5382insC and 6174delT mutations; breast cancer; ovarian cancer

References


Maksimov, S.Y., Khajymba, A.V., Katamadze, I.G. Ovarian cancer at polyneoplasia syndrome of the reproductive system organs. Materials of the scientific conference “New approaches to screening, diagnostics and treatment of ovarian cancer.” Veliky Novgorod, May 17–18, 2001. St.-Petersburg (2001): 85 p.

Shchepotin, I.B., Zotov, A.V., Engel, O.T. “Primary multiple malignant tumors of the female reproductive system.” Oncology 11.4 (2009): 249–53.

Pruthi, S., Gostout, B.S., Lindor, N.M. “Identification and Management of Women with BRCA Mutations or Hereditary Predisposition for Breast and Ovarian Cancer.” Mayo Clinic Proceedings 85.12 (2010): 1111–20.

Meindl, A., Ditsch, N., Kast, K., et al. “Hereditary breast and ovarian cancer: new genes, new treatments, new concepts.” Dtsch Arztebl Int 108.19 (2011): 323–30.

Kim, M.K., Song, S.Y., Do, I.G., et al. ”Synchronous gynecologic malignancy and preliminary results of Lynch syndrome.” J Gynecol Oncol 22 (2011): 233–8.

Liu, S., Ginestier, C., Charafe-Jauffret, E., et al. “BRCA1 regulates human mammary stem/progenitor cell fate.” Proc Natl Acad Sci USA 105 (2008): 1680–5.

Kang, H.J., Yi, Y.W., Kim, H.J., et al. “BRCA1 negatively regulates IGF-1 expression through an estrogen-responsive element-like site.” Cell Death Dis12.3 (2012): 336. DOI: 10.1038/cddis.2012.78

Wang, L., Di, L.-J. “BRCA1 аnd Estrogen/Estrogen Receptor In Breast Cancer: Where They Interact?” Int J Biol Sci 10.5 (2014): 566–75.

Lakhani, S.R., Vijver, M.J., Jacquemier, J., et al. “The Pathology of Familial Breast Cancer: Predictive Value of Immunohistochemical Markers Estrogen Receptor, Progesterone Receptor, HER-2, and p53 in Patients With Mutations in BRCA1 and BRCA2.” J Clin Oncol 20.9 (2012): 2310–18.

Kwon, J.S., Tinker, A., Pansegrau, G., et al. “Prophylactic Salpingectomy and Delayed Oophorectomy as an Alternative for BRCA Mutation Carriers.” Obstetrics and gynecology 121.1 (2013): 14–24.

Roukos, D.H., Briasoulis, E. “Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome.” Nature Clinical Practice Oncology 4 (2007): 578–90.


GOST Style Citations


1. Максимов, С.Я., Хаджимба, А.В., Катамадзе, И.Г. Рак яичников в синдроме полинеоплазий органов репродуктивной системы : материалы научной конференции «Новые подходы к скринингу, диагностике и лечению опухолей яичников», г. Великий Новгород, 17–18 мая 2001 г. – Санкт-Петербург, 2001. – 85 с.

2. Щепотін, І.Б. Первинно-множинні злоякісні пухлини органів жіночої репродуктивної системи / І.Б. Щєпотін, О.В. Зотов, О.Т. Енгел // Онкологія. – 2009. – № 11 (4). – С. 249–53.

3. Pruthi, S., Gostout, B.S., Lindor, N.M. “Identification and Management of Women with BRCA Mutations or Hereditary Predisposition for Breast and Ovarian Cancer.” Mayo Clinic Proceedings 85.12 (2010): 1111–20.

4. Meindl, A., Ditsch, N., Kast, K., et al. “Hereditary breast and ovarian cancer: new genes, new treatments, new concepts.” Dtsch Arztebl Int 108.19 (2011): 323–30.

5. Kim, M.K., Song, S.Y., Do, I.G., et al. ”Synchronous gynecologic malignancy and preliminary results of Lynch syndrome.” J Gynecol Oncol 22 (2011): 233–8.

6. Liu, S., Ginestier, C., Charafe-Jauffret, E., et al. “BRCA1 regulates human mammary stem/progenitor cell fate.” Proc Natl Acad Sci USA 105 (2008): 1680–5.

7. Kang, H.J., Yi, Y.W., Kim, H.J., et al. “BRCA1 negatively regulates IGF-1 expression through an estrogen-responsive element-like site.” Cell Death Dis12.3 (2012): 336. DOI: 10.1038/cddis.2012.78

8. Wang, L., Di, L.-J. “BRCA1 аnd Estrogen/Estrogen Receptor In Breast Cancer: Where They Interact?” Int J Biol Sci 10.5 (2014): 566–75.

9. Lakhani, S.R., Vijver, M.J., Jacquemier, J., et al. “The Pathology of Familial Breast Cancer: Predictive Value of Immunohistochemical Markers Estrogen Receptor, Progesterone Receptor, HER-2, and p53 in Patients With Mutations in BRCA1 and BRCA2.” J Clin Oncol 20.9 (2012): 2310–18.

10. Kwon, J.S., Tinker, A., Pansegrau, G., et al. “Prophylactic Salpingectomy and Delayed Oophorectomy as an Alternative for BRCA Mutation Carriers.” Obstetrics and gynecology 121.1 (2013): 14–24.

11. Roukos, D.H., Briasoulis, E. “Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome.” Nature Clinical Practice Oncology 4 (2007): 578–90.





DOI: https://doi.org/10.18370/2309-4117.2016.27.68-71

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2411-1295 (Online), ISSN 2309-4117 (Print)