Inactivation of BRCA1, BRCA2 and p53 Genes in Sporadic Ovarian Cancer
Authors:
Michal Zikán 1
; P. Pohlreich 2; P. Freitag 1; M. Janoušek 1; D. Pavlišta 1
; D. Fischerová 1; N. Jančárková 1; J. Sláma 1; I. Pinkavová 1; D. Cibula 1
Authors place of work:
Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a VFN, Praha, přednosta prof. MUDr. A. Martan, DrSc.
1; Ústav biochemie a experimentální onkologie 1. LF UK, přednosta prof. MUDr. A. Šedo, DrSc.
2
Published in the journal:
Ceska Gynekol 2008; 73(5): 298-302
Category:
Original Article
Summary
Objective:
To analyze loss of heterozygosity (LOH), loss of expression and somatic mutations of BRCA1, BRCA2 and p53 genes in sporadic epithelial ovarian cancer samples.
Design:
Original paper.
Setting:
Oncogynecologic center, Clinic of Obstetrics and gynecology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital, Prague.
Material and methods:
We used genomic DNA and total RNA from peripheral blood and fresh frozen tumor as a template for LOH, loss-of-expression and mutation analyses.
Results:
LOH in at least one region was found in 60% of tumors. Majority of these alterations occurred not solely, but in conjunction with other region deletions.
Conclusion:
Our study confirms high frequency of somatic alteration of BRCA1, BRCA2 and p53 genes in sporadic epithelial ovarian cancer.
Key words:
BRCA1, BRCA2, p53, ovarian cancer, LOH.
Zdroje
1. Chan, K., Ozcelik, H., Cheung, A., et al. Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer. Cancer Res, 2002, 62, p. 4151-4156.
2. Eltabbakh, GH., Belinson, JL., Kennedy, AW., et al. p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer. Cancer, 1997, 80, 5, p. 892-898.
3. Esteller, M., Silva, J., Dominguez, G., et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst, 2000, 92, 7, p. 564-569.
4. Geisler, J., Rathe, J., Hattermann-Zogg, M., et al. BRCA1 dysfunction is common in ovarian cancer. J Natl Cancer Inst, 2004, 94, p. 61-67.
5. Gras, E., Cortes, J., Diez, O., et al. Loss of heterozygosity on chromosome 13q12-q14, BRCA-2 mutations and lack of BRCA-2 promoter hypermethylation in sporadic epithelial ovarian tumors. Cancer, 2001, 92, p. 787-795.
6. Herod, JJ., Eliopoulos, AG., Warwick, J. The prognostic significance of Bcl-2 and p53 expression in ovarian carcinoma. Cancer Res, 1996, 56, 9, p. 2178-2184.
7. Hilton, J., Geisler, J., Rathe, J., et al. Inactivation of BRCA1 and BRCA2 in ovarian cancer. J Natl Cancer Inst, 2002, 94, p. 1396-1406.
8. Janatova, M., Pohlreich, P., Matous, B. Detection of the most frequent mutations in BRCA1 gene on polyacrylamide gels containing Spreadex Polymer NAB. Neoplasma, 2003, 50, 4, p. 246-250.
9. Janatova, M., Zikan, M., Dundr, P., et al. Novel somatic mutations in the BRCA1 gene in sporadic breast tumors. Hum Mutat, 2005, 25, 3, p. 319.
10. Kupryjanczyk, J., Thor, AD., Beauchamp, R., et al. p53 gene mutations and protein accumulation in human ovarian cancer. Proc Natl Acad Sci, 1993, 90, p. 4961-4965.
11. McCoy, M., Mueller, C., Roskelley, C. The role of the breast cancer susceptibility gene 1 (BRCA1) in sporadic epithelial ovarian cancer. Reprod Biol Endocrin, 2003, 1, p. 72.
12. Miyamoto, K., Fukutomi, T., Asada, K., et al. Promoter hypermethylation and post-transcriptional mechanisms for reduced BRCA1 immunoreactivity in sporadic human breast cancers. Jpn J Clin Oncol, 2002, 32, 3, p. 79-84.
13. Szabo, C., King, MC. Population genetics of BRCA1 and BRCA2. Am J Hum Genet, 1997, 60, p. 1013-1020.
14. Takahashi, H., Chiu, H., Bandera, C., et al. Mutations of the BRCA2 gene in ovarian carcinomas. Cancer Res, 1996, 56, p. 2738-2741.
14. Verma, M., Srivastava, S. Epigenetics in cancer: implications for early detection and prevention. Lancet Oncol, 2002, 3, p. 755-763.
15. Zikan, M., Pohlreich, P., Stribrna, J. Mutational analysis of the BRCA1 gene in 30 Czech ovarian cancer patients. J Genet, 2005, 84, 1, p. 63-67.
16. Zikan, M., Pohlreich, P., Stribrna, J. Novel complex genomic rearrangement of the BRCA1 gene. Mutat Res, 2007 (doi:10.1016/j.mrfmmm.2007.08.002).
Štítky
Paediatric gynaecology Gynaecology and obstetrics Reproduction medicineČlánok vyšiel v časopise
Czech Gynaecology
2008 Číslo 5
Najčítanejšie v tomto čísle
- Long-term Low Molecular Weight Heparin Protection during Pregnancy for the Recurrent Fetal Loss
- Myoms, Fertility and Pregnancy
- Caesarean Section – Indication or Choice?
- Vaginal and Postpregnancy Inflamations, Risks of their Treatment for Fetus