Loss of Heterozygosity in BRCA1 and BRCA2 Genes in Patients with Ovarian Cancer and Probability of Its Use for Clinical Classification of Variations
- 作者: Kechin A.1, Boyarskikh U.2, Ermolenko N.2, Tyulyandina A.3, Lazareva D.4, Avdalyan A.4, Tyulyandin S.3, Kushlinskii N.3, Filipenko M.2
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隶属关系:
- Novosibirsk State University
- Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences
- N. N. Blokhin National Medical Research Center of Oncology, the Ministry of Health of Russia
- Altai Territorial Cancer Control Center
- 期: 卷 165, 编号 1 (2018)
- 页面: 94-100
- 栏目: Article
- URL: https://journals.rcsi.science/0007-4888/article/view/240017
- DOI: https://doi.org/10.1007/s10517-018-4107-9
- ID: 240017
如何引用文章
详细
Changes (or variants) in BRCA1 and BRCA2 gene sequences can have different lengths and clinical significance: from single nucleotide variants (SNV) and short insertions/deletions (<50 bp) to extended deletions and duplications (so-called copy number variations, or CNV). According to their clinical significance, all variants can be divided into pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign. Moreover, variants can be germinal (i.e. inherited from parents) and somatic (arising in the process of development of the organism). A specific somatic event is loss of heterozygosity (LOH), i.e. transition of one or many point and short variants from heterozygous to homozygous state. Such an event can be the key to the development of carcinogenesis for cells carrying a pathogenic variant, if we consider it within the framework of the Knudson’s two-hit carcinogenesis theory. We studied the prevalence and nature of LOH in of ovarian cancer samples carrying or not carrying a pathogenic variant. To this end, a full coding sequence of BRCA1/2 genes was determined in 30 pairs of DNA samples isolated from blood cells and paraffinized histological blocks of patients on a MiSeq Illumina instrument. Analyss of the obtained reads revealed 9 pathogenic point and short variants (30% patients): 6 germinal (20%) and 3 somatic (10%), and 8 somatic CNV (3 deletions and 5 duplications of several or all exons of the BRCA1 gene). LOH was detected in 70% patients; among the carriers of pathogenic variants - in 83%. For pathogenic variants, the percentage of reads with the alternative allele increased more often than for benign variants located in another gene, or detected in other patients (67% vs. 44%). However, the difference was statistically insignificant, which can be due to insufficient number of patients. Only in 3 of 21 cases of LOH (14%), it can be attributed to CNV. In other cases, LOH is most likely determined by gene conversion, but further research is needed.
作者简介
A. Kechin
Novosibirsk State University
编辑信件的主要联系方式.
Email: a.a.kechin@gmail.com
俄罗斯联邦, Novosibirsk
U. Boyarskikh
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences
Email: a.a.kechin@gmail.com
俄罗斯联邦, Novosibirsk
N. Ermolenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences
Email: a.a.kechin@gmail.com
俄罗斯联邦, Novosibirsk
A. Tyulyandina
N. N. Blokhin National Medical Research Center of Oncology, the Ministry of Health of Russia
Email: a.a.kechin@gmail.com
俄罗斯联邦, Moscow
D. Lazareva
Altai Territorial Cancer Control Center
Email: a.a.kechin@gmail.com
俄罗斯联邦, Barnaul
A. Avdalyan
Altai Territorial Cancer Control Center
Email: a.a.kechin@gmail.com
俄罗斯联邦, Barnaul
S. Tyulyandin
N. N. Blokhin National Medical Research Center of Oncology, the Ministry of Health of Russia
Email: a.a.kechin@gmail.com
俄罗斯联邦, Moscow
N. Kushlinskii
N. N. Blokhin National Medical Research Center of Oncology, the Ministry of Health of Russia
Email: a.a.kechin@gmail.com
俄罗斯联邦, Moscow
M. Filipenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences
Email: a.a.kechin@gmail.com
俄罗斯联邦, Novosibirsk