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Methylation of the RASSF1A, RARβ2, and SEMA3B genes in epithelial breast and ovarian tumors, and in patients with polyneoplasia

https://doi.org/10.17650/1994-4098-2012-0-1-61-68

Abstract

The methylation status of the tumor suppressor genes RASSF1A, RARβ2, and SEMA3B was studied in the samples of cancer and its histologically normal tissue of the breast and ovaries. The high rate of abnormal methylation of the CpG islet in the RASSF1A, RARβ2, and SEMA3B genes was found in the tumors of the breast (78% (32/41), 46% (26/56), and 35% (22/65), respectively) and ovaries 73% (33/45), 30% (15/50), and 50% (25/51). Hypermethylation in the CpG islets belonging to the RASSF1A and RARβ2 genes was first ascertained in 90% of the patients with polyneoplasms involving the breast and ovaries. Abnormal methylation of the promotor region of the RASSF1A gene was shown to be detectable in preclinical-stage and anaplasia-degree breast and ovarian cancer. There was a correlation of the rate of methylation in the promoter regions of the RARβ2 and SEMA3B genes with clinical-stage and anaplasia-degree breast and ovarian cancer. Analysis of gene methylation in biological fluids provides considerable opportunity to use methylation of DNA as a marker in clinical practice.

About the Authors

T. P. Kazubskaya
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation


V. I. Loginov
State Research Center, State Research Institute of Genetics, Moscow
Russian Federation


D. S. Khodyrev
State Research Center, State Research Institute of Genetics, Moscow
Russian Federation


V. D. Ermilova
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation


Yu. G. Payanidi
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation


N. V. Chkhikvadze
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation


V. Yu. Selchuk
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation


E. A. Braga
State Research Center, State Research Institute of Genetics, Moscow
Russian Federation


References

1. Минимальные клинические рекомендации Европейского общества медицинской онкологии (ESMO). М., 2009.

2. Pharoah P.D., Antoniou A., Bobrow M. et al. Polygenic 48 susceptibility to breast cancer and implications for prevention. Nat Genet 2002;31:33–6.

3. Narod S.A., Foulkes W.D. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 2004;(9):665–76.

4. Galper S., Gelman R., Recht A. et al. Second non-breast malignancies after conservative surgery and radiation therapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys 2002;52:406–14.

5. Dammann R., Li C., Yoon J.H. et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet 2000; 25:315–9.

6. Имянитов Е.Н., Хансон К.П. Молеку- лярная онкология: клинические аспекты. СПб., 2007.

7. Clark S.J., Harrison J., Paul C.L., Frommer M. High sensitivity mapping of methylated cytosines. Nucl Acids Res 1994;22:2990–7.

8. Ivanova T., Petrenko A., Gritsko T. et al. Methylation and silencing of the retinoic acid receptor-в2 gene in cervical cancer. BMC Cancer 2002;2:4–11.

9. Dreijerink K., Braga E., Kuzmin I. et al. The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Proc Natl Acad Sci 2001;98:7504–9.

10. Dammann R., Schagdarsurengin U., Seidel C. et al. The tumor suppressor RASSF1A in human carcinogenesis: an update. Histol Histopathol 2005; 20(2):645–66.

11. Lerman M.I., Minna J.D. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. Cancer Res 2000;60(21):6116–33.

12. Логинов В.И., Малюкова А.В., Серегин Ю.А. и др. Уровень метилирования гена RASSF1A в эпителиальных опухолях почки, молочной железы и яичников. Мол биол 2004; 38:654–67.

13. Брага Э.А., Киселев Л.Л., Забаровский Е.Р. От идентификации геномных полиморфизмов к диагностическим и прогностическим маркерам эпителиальных опухолей человека. Мол биол 2004;38:179–90.

14. Angeloni D. Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease. Brief Funct Genom Proteom 2007;6(1):19–39.

15. Tomizawa Y., Kohno T., Kondo H., Otsuka A. et al. Clinicopathological signifycance of epigenetic inactivation of RASSF1A at 3p21.3 in stage I lung adenocarcinoma. Clin Cancer Res 2002; 8:2362–8.


Review

For citations:


Kazubskaya T.P., Loginov V.I., Khodyrev D.S., Ermilova V.D., Payanidi Yu.G., Chkhikvadze N.V., Selchuk V.Yu., Braga E.A. Methylation of the RASSF1A, RARβ2, and SEMA3B genes in epithelial breast and ovarian tumors, and in patients with polyneoplasia. Tumors of female reproductive system. 2012;(1):61-68. (In Russ.) https://doi.org/10.17650/1994-4098-2012-0-1-61-68

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ISSN 1994-4098 (Print)
ISSN 1999-8627 (Online)