dc.contributor.author |
Brovkina O. |
|
dc.contributor.author |
Shigapova L. |
|
dc.contributor.author |
Chudakova D. |
|
dc.contributor.author |
Gordiev M. |
|
dc.contributor.author |
Enikeev R. |
|
dc.contributor.author |
Druzhkov M. |
|
dc.contributor.author |
Khodyrev D. |
|
dc.contributor.author |
Shagimardanova E. |
|
dc.contributor.author |
Nikitin A. |
|
dc.contributor.author |
Gusev O. |
|
dc.date.accessioned |
2019-01-22T20:54:52Z |
|
dc.date.available |
2019-01-22T20:54:52Z |
|
dc.date.issued |
2018 |
|
dc.identifier.uri |
https://dspace.kpfu.ru/xmlui/handle/net/149393 |
|
dc.description.abstract |
© 2018 Frontiers Media S.A. All Rights Reserved. The Russian population consists of more than 100 ethnic groups, presenting a unique opportunity for the identification of hereditary pathogenic mutations. To gain insight into the landscape of heredity pathogenic variants, we employed targeted next-generation sequencing to analyze the germline mutation load in the DNA damage response and repair genes of hereditary breast and ovary cancer syndrome (HBOCS) patients of Tatar ethnicity, which represents ∼4% of the total Russian population. Several pathogenic mutations were identified in DNA double-strand break repair genes, and the spectrum of these markers in Tatar patients varied from that previously reported for patients of Slavic ancestry. The CDK12 gene encodes cyclin-dependent kinase 12, the key transcriptional regulator of the genes involved in DNA damage response and repair. CDK12 analysis in a cohort of HBOCS patients of Tatar decent identified a c.1047-2A>G nucleotide variant in the CDK12 gene in 8 of the 106 cases (7.6%). The c.1047-2A>G nucleotide variant was identified in 1 of the 93 (1.1%) HBOCS patients with mixed or unknown ethnicity and in 1 of the 238 (0.42%) healthy control patients of mixed ethnicity (Tatars and non-Tatars) (p = 0.0066, OR = 11.18, CI 95% = 1.53-492.95, Tatar and non-Tatar patients vs. healthy controls). In a group of mixed ethnicity patients from Tatarstan, with sporadic breast and/or ovarian cancer, this nucleotide variant was detected in 2 out of 93 (2.2%) cases. In a cohort of participants of Slavic descent from Moscow, comprising of 95 HBOCS patients, 80 patients with sporadic breast and/or ovarian cancer, and 372 healthy controls, this nucleotide variant was absent. Our study demonstrates a strong predisposition for the CDK12 c.1047-2A>G nucleotide variant in HBOCS in patients of Tatar ethnicity and identifies CDK12 as a novel gene involved in HBOCS susceptibility. |
|
dc.subject |
BRCA1 |
|
dc.subject |
BRCA2 |
|
dc.subject |
Breast cancer |
|
dc.subject |
CDK12 |
|
dc.subject |
Homologous recombination repair |
|
dc.subject |
Next-generation sequencing |
|
dc.subject |
Ovarian cancer |
|
dc.title |
The ethnic-specific spectrum of germline nucleotide variants in DNA damage response and repair genes in hereditary breast and ovarian cancer patients of Tatar descent |
|
dc.type |
Article |
|
dc.relation.ispartofseries-issue |
OCT |
|
dc.relation.ispartofseries-volume |
8 |
|
dc.collection |
Публикации сотрудников КФУ |
|
dc.source.id |
SCOPUS-2018-8--SID85055321576 |
|