201P - CDK12 – new breast and ovarian cancer predisposition gene in Tatar population?

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Ovarian Cancer
Breast Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Elena Shagimardanova
Citation Annals of Oncology (2017) 28 (suppl_5): v43-v67. 10.1093/annonc/mdx362
Authors E. Shagimardanova1, O. Brovkina2, M. Gordiev3, R. Enikeev4, L. Shigapova1, D. Khodyrev2, O. Gusev1, A. Kedrova2, V. Kosiy2, A. Nikitin2
  • 1Extreme Biology Laboratory, Kazan Volga Region Federal University, 420008 - Kazan/RU
  • 2Molecular Genetic Laboratory, Federal Research and Clinical Center, FMBA of Russia, 115682 - Moscow/RU
  • 3Laboratory, Tatarstan Cancer Center, Kazan/RU
  • 4Chemotherapy, Kazan Clinical Oncology Center, 420029 - Kazan/RU



The development of hereditary ovarian and breast cancer (OC/BC) is often caused by genetic defects in the DNA repair system. However, the diagnostics in most medical centers of Russia includes PCR-based identification only the eight common mutations in BRCA1/2 for the Slavic population. Previously we established that patients of the Tatar population with OC/BC did not possess most of Slavic mutation and a significant part of the predisposition is due to other mutations in the genes of the homologous recombination (HR) system. The aim of this work is the analysis of the germline mutations in the HR genes.


The DNA from 175 blood samples from patients of the Volga District with hereditary OC/BC were analyzed by targeted NGS (Roche NimbleGen, Illumina MiSeq), the comparison groups included blood samples from patients of Slavic origin.


62% of the detected pathogenic mutations were presented in the BRCA1/2 genes. The remaining mutations were found in other genes of the reparation system (HGMD Professional 2017.1 database). An unexpected finding was the detection of a germline splicing mutation c.1047-2A>G in CDK12 gene (Chr17(GRCh37):37627130A>G, NM_016507.3) in patients of Tatar origin (Table).Table:

201P CDK12 c.1047-2A>G frequency distribution

Subjects origin BC or OC Healthy controls
Tatar from Volga District 6/94 (6.4%) 0/32 (0%)
Non-Tatar from Volga District 1/81 (1.2%)
Slavic from Moscow 0/49 (0%) 0/284 (0%)
ExAC NFE 29/64446 (0.045%)
1000G 2/5006 (0.039%)

Mutation c.1047-2A>G is more common in patients with OC/BC in comparison with healthy controls (7/224 vs 0/316, p = 0.002, OR = 21.49, CI 95% = 1.22–377.25).


Gene CDK12 is one of the most frequently altered genes in serous ovarian cancers, but significance of CDK12 germline mutations in hereditary cancers remains to be defined. Its role in carcinogenesis of OC was established recently and CDK12 was not included in most NGS panels of HR genes. Our study demonstrates that CDK12 may be novel candidate gene for OC/BC genetic predisposition. Notably, frequency of CDK12 c.1047-2A>G (6.4%) mutation is comparable with frequency of founder-mutation BRCA1 5382insC (7.4%), that indicates its possible founder role in Tatar population.

Clinical trial identification

Legal entity responsible for the study

Tatarstan Cancer Center


Kazan (Volga Region) Federal University, Tatarstan Cancer Center


All authors have declared no conflicts of interest.