№ 5 / 2016 / 20-27

Detection of polymorphism of rs78378222 gene TP53 in tumor tissue of diffuse large B-cell lymphoma

Author: Pospelova T.I.¹, Voevoda M.I.², Voropaeva E.N.³, Maksimov V.N.⁴, Beresina O.V.⁵, Kovynev I.B.⁶, Marinkin I.O.⁷

Abstract

rs78378222 gene TP53 is under negative natural selection, and malignant neoplasms are the selection mechanism. OBJECTIVE: to reveal the frequency of rs78378222 gene TP53 in tumor tissue of Diffuse large B-cell lymphoma (DLBCL). Material and methods. Genomic DNA was isolated by phenol-chloroform extraction using guanidine from paraffin blocks of lymph node and extranodal tumor lesions biopsies of 92 patients with DLBCL. The tissue sections containing at least 80–90 % of the tumor cells were investigated. Genotyping of rs78378222 in TP53 gene was performed by PCR RFLP analysis. To confirm the presence of rare allele C rs78378222 the direct sequencing by Sanger was performed. Results and discussion. The frequency of rs78378222 in DLBCL tumor tissue was 9/92 (9.8 %). It has been noted that minor allele C in the homozygous state was revealed in 5 from 9 patients. Since the detection of cases of the rare homozygous genotype C/C rs78378222 in normal tissue is not described, the results indicate a loss of heterozygosity in the TP53 gene in DLBCL tumor tissue. The phenomenon of loss of heterozygosity in the TP53 gene in carriers of the heterozygous genotype A/C rs78378222 in tumor tissue DLBCL is an example of the classic «two-hit» carcinogenesis mechanism described by Knudsen.

Key words

DLBCL, carcinogenesis, rs78378222, sequencing, Knudsen theory

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About Authors (Correspondence):

Pospelova T.I. – doctor of medical sciences, professor, head of the chair for therapy, hematology and transfusiology, е-mail: postatgem@mail.ru

Voevoda M.I. – corresponding member of RAS, doctor of medical sciences, professor, director, е-mail: mvoevoda@ya.ru

Voropaeva E.N. – candidate of medical sciences, researcher of the laboratory of molecular-genetic methods of study of the therapeutic diseases, е-mail: vena.81@mail.ru

Maksimov V.N. – doctor of medical sciences, professor, head of the laboratory of molecular-genetic methods of study of the therapeutic diseases, е-mail: medik11@mail.ru

Beresina O.V. – candidate of medical sciences, assistant professor of the chair for therapy, hematology and transfusiology, е-mail: ovberezina@mail.ru

Kovynev I.B. – doctor of medical sciences, professor of the chair for therapy, hematology and transfusiology, е-mail: kovin_gem@mail.ru

Marinkin I.O. – doctor of medical sciences, professor, rector, е-mail: rector@ngmu.ru

Received: 08/11/2016