Mutation 6174delT in the BRCA2 gene in men with prostate cancer in Ukraine

  • I. V. Gorodetska
  • S. V. Serga
  • E. O. Stakhovsky
  • O. A. Kononenko
  • O. E. Stakhovsky
  • M. V. Pikul
  • S. V. Demydov
  • I. A. Kozeretska

Abstract

Aim. Mutations in BRCA1/2 genes are known to increase the risk of human breast cancer, pancreatic cancer and prostate cancer. In Ukraine only mutations in woman BRCA1/2 were studied, thus the situation with these diseases related to disturbance of these genes in Ukrainian men remains poorly explored. 6174delT is a frameshift mutation and is results in stop of transcription and translation of the functional protein BRCA2. Methods. Genomic DNA was purified from peripheral blood.We performed PCR analysis of 116 DNA from men with prostate cancer in order to detect presence of mutation in BRCA2 gene (6174delT). To detect the mutation by mutagenically separated PCR, we used two PCR reactions. The first reaction used one general primer and one primer specific to the mutation, and the second reaction was with one general primer and one primer specific to the wild type allele. Results. Among screened samples no mutations in the BRCA2 gene were found in prostate cancer patients. Conclusions. Our results suggest that the incidence of this event is not more than 0.9% among men with prostate cancer inUkraine.

Keywords: mutation, 6174delT, BRCA2, prostate cancer, Ukraine.

References

Cavanagh H., Rogers Katherine M.A. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hered Cancer Clin Pract. 2015. Vol. 13. P. 16. doi: 10.1186/s13053-015-0038-x.

Fentiman I.S., Fourquet A., Hortobagyi G.N. Male breast cancer. The Lancet. 2006. Vol. 367. P. 595–604. doi: 10.1016/S0140-6736(06)68226-3.

Venkitaraman Ashok R. Functions of BRCA1 and BRCA2 in the biological response to DNA damage. Journal of Cell Science. 2001. Vol. 114. P. 3591–3598.

Boulton S.J. Cellular functions of the BRCA tumour-suppressor proteins. Biochemical Society Transactions. 2006. Vol. 34. P. 633–645. doi: 10.1042/BST0340633.

Gorodetska I.V., Serga S.V., Levkovich N.M., Lahuta T.I., Anikusko N.F., Tymovska Yu.O., Cheshuk V.Ie., Smolanka I.I., Sklyar S.Yu., Polenkov S.E., Boichenko O.I., Demydov S.V., Zhuk O.W., Kozeretska I.A. The frequency of BRCA1 founder mutation c.5266dupC (5382insC) in breast cancer patients from Ukraine. Hered Cancer Clin Pract. 2015. Vol. 13. P. 19. doi: 10.1186/s13053-015-0040-3.

Gorodetska I., Serga S., Lahuta T., Ostapchenko L., Demydov S., Khranovska N., Skachkova O., Inomistova M., Kolesnik O., Svintsitsky V., Tsip N., Peresunko A., Kmit’ N., Manzhura O., Rossokha Z., Popova O., Salomakhina H., Kyriachenko S., Kozeretska I. Prevalence of two BRCA1 mutations, 5382insC and 300T>G, in ovarian cancer patients from Ukraine. Familial Cancer. 2017. Vol. 16. P. 471–476. doi: 10.1007/s10689-017-9978-9.

Thompson D., Easton D.F. Cancer incidence in BRCA1 mutation carriers. Journal of the National Cancer Institute. 2002. Vol. 94. P. 1358–1365.

Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, Tung N, Horsman D, Isaacs C, Monteiro AN, Sun P, Narod SA. Cancer variation associated with the position of the mutation in the BRCA2 gene. Familial Cancer. 2004. Vol. 3. P. 1–10. doi: 10.1023/B:FAME.0000026816.32400.45.

Chan PC, Wong BY, Ozcelik H, Cole DE. Simple and Rapid Detection of BRCA1 and BRCA2 Mutations by Multiplex Mutagenically Separated PCR. Clinical Chemistry. 1999. Vol. 45. P. 1285–1287.

Bancroft EK, Page EC, Castro E, et al. Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study. European urology. 2014. Vol. 65. P. 0302–2838. doi: 10.1016/j.eururo.2014.01.003.

I Agalliu, E Karlins, E M Kwon, L M Iwasaki, A Diamond, E A Ostrander, and J L Stanford. Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer. British Journal of Cancer. 2007. Vol. 97. P. 826–831. doi: 10.1038/sj.bjc.6603929.

Gayther SA, de Foy KA, Harrington P, Pharoah P, Dunsmuir WD, Edwards SM, Gillett C, Ardern-Jones A, Dearnaley DP, Easton DF, Ford D, Shearer RJ, Kirby RS, Dowe AL, Kelly J, Stratton MR, Ponder BA, Barnes D, Eeles RA. The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. Cancer Research. 2000. Vol. 60. P. 2115–2121.