SINGLE NUCLEOTIDE POLYMORPHISMS IN BREAST TUMOR AND EXPRESSION OF ABC-TRANSPORTERS AFTER NEOADJUVANT CHEMOTHERAPY
Abstract
The mechanism of regulation of ABC transporter gene expression, which is related to individual characteristics of the tumor-bearing organism and its tumor, defined by gene single nucleotide polymorphisms (SNP – Single Nucleotide Polymorphism) has not been extensively studied. We conducted large-scale genome studies of association of SNP with the level of ABC transporter gene expression. The study involved 68 patients with morphologically verified diagnosis of breast cancer treated with neoadjuvant chemotherapy (NAC). Using a quantitative Real-time PCR, the expression of 4 multidrug resistence (MDR) genes (ABCB1, ABCC1, ABCC2, ABCG2) was studied in surgical samples after NAC. Microarray analysis was performed using high density DNA microarrays, which contain more than 750.000 SNPs. Six SNPs significantly associated with postoperative expression levels of multidrug resistance genes, ABCB1, ABCC1, ABCC2, ABCG2, were identified. It was shown that in carriers of a rare genotype, the expression levels of all 4 examined genes in tumors after chemotherapy were either decreased (rs2680835, rs1951366 and rs12018988), or increased (rs4676478, rs6896596, rs1154121) compared to those observed in carriers of frequent and heterozygous genotypes of the SNP. The possible mechanisms of the effect of the identified SNPs and their genes on the expression of ABC transporters were discussed.
About the Authors
M. M. Tsyganov
Tomsk Саnсеr Rеsеаrсh Institute
Russian Federation
Russian Federation
Tsyganov Matvey Mikhailovich, junior research fellow, Laboratory of Viral Oncology.
Phone: +7 (3822) 51-46-09. E-mail: TsyganovMM@yandex.ru. SPIN-code: 1253-0240
M. K. Ibragimova
Tomsk Саnсеr Rеsеаrсh Institute
Russian Federation
Russian Federation
Ibragimova Marina Konstantinovna, junior research fellow, Laboratory of Viral Oncology.
Phone: +7 (3822) 51-46-09. E-mail: imk1805@yandex.ru. SPIN-code: 2340-1628
E. M. Slonimskaya
Tomsk Саnсеr Rеsеаrсh Institute
Russian Federation
Russian Federation
Slonimskaya Elena Mikhailovna, MD, Professor, Head of General Oncology Department.
Phone: +7 (3822) 41-80-92. E-mail: slonimskaya@rambler.ru. SPIN-code: 7763-6417
N. V. Cherdyntseva
Tomsk Саnсеr Rеsеаrсh Institute
Russian Federation
Russian Federation
Cherdyntseva Nadezhda Viktorovna, Professor, Deputy Director for Basic Science, Head of Laboratory of Molecular Oncology and Immunology.
Phone: +7 (3822) 51-53-42. E-mail: nvch@oncology. tomsk.ru. SPIN-code: 5344-0990
N. V. Litviakov
Tomsk Саnсеr Rеsеаrсh Institute
Russian Federation
Russian Federation
Litviakov Nikolay Vasilyevich, DSc, Head of Laboratory of Viral Oncology.
Phone: +7 (3822) 51-46-07. E-mail: nvlitv72@yandex.ru. SPIN-code: 2546-0181
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Review
For citations:
Tsyganov M.M., Ibragimova M.K., Slonimskaya E.M., Cherdyntseva N.V., Litviakov N.V. SINGLE NUCLEOTIDE POLYMORPHISMS IN BREAST TUMOR AND EXPRESSION OF ABC-TRANSPORTERS AFTER NEOADJUVANT CHEMOTHERAPY. Siberian journal of oncology. 2015;1(5):59-66. (In Russ.)
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