25P - Breast cancer predisposing germline mutations identified by exome sequencing

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Breast Cancer
Aetiology, epidemiology, screening and prevention
Personalised/Precision medicine
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Ekaterina Kuligina
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors E.S. Kuligina1, A.P. Sokolenko1, I.V. Bizin2, M.O. Anisimova1, A.A. Romanko1, E. Imyanitov1
  • 1Department Of Tumor Biology, NN Petrov Research Institute of Oncology, 197758 - Saint Petersburg/RU
  • 2Bioinformatics, St. Petersburg State Polytechnical University, Saint Petersburg/RU



A significant portion of hereditary predisposition to breast cancer (BC) is attributed to yet unknown factors. Russian population is characterized by surprisingly strong founder effect, therefore whole exome sequencing (WES) for a limited number of these genetically homogenous patients has a potential to identify novel BC-predisposing genes.


WES was performed for 32 Russian BC cases, which demonstrated strong clinical signs of the hereditary disease (family history, BC bilaterality, young onset) and lacked germline mutations in “canonical” BC genes (BRCA1, BRCA2, CHEK2, PALB2, and NBS1/NBN).


Eight patients carried potentially pathogenic mutations in BRCA1 network genes (3 truncations (BLM p.Q548*, RAD51C c.904 + 1G>A, FANCM p.S497fs) and 5 missense mutations (FANCM (p.R100W, p.Q891P), ERCC4 p.R799W, RAD54L p.R394W, RAD50 p.D515G)). The remaining 24 patients were analyzed for the presence of rare non-silent genetic variants; in total, 15437 alleles had ExAC frequency


This study revealed several alleles, which may be associated with increased BC predisposition. However, in contrast to well-known Slavic BRCA founder mutations, newly identified candidates are exceptionally rare and therefore are unlikely to be responsible for a significant share of BC morbidity. Supported by the RSF grant No 16-45-02011

Clinical trial identification

Legal entity responsible for the study

Evgeny N. Imyanitov, Head of the Department of Tumor Biology in the N.N. Petrov Institute of Oncology


Russian Scientific Fund (grant No 16-45-02011).


All authors have declared no conflicts of interest.