title: Identification of novel hereditary cancer genes by whole exome sequencing.
abstract: Whole exome sequencing (WES) provides a powerful tool for medical genetic research. Several dozens of WES studies involving patients with hereditary cancer syndromes have already been reported. WES led to breakthrough in understanding of the genetic basis of some exceptionally rare syndromes; for example, identification of germ-line SMARCA4 mutations in patients with ovarian hypercalcemic small cell carcinomas indeed explains a noticeable share of familial aggregation of this disease. However, studies on common cancer types turned out to be more difficult. In particular, there is almost a dozen of reports describing WES analysis of breast cancer patients, but none of them yet succeeded to reveal a gene responsible for the significant share of missing heritability. Virtually all components of WES studies require substantial improvement, e.g. technical performance of WES, interpretation of WES results, mode of patient selection, etc. Most of contemporary investigations focus on genes with autosomal dominant mechanism of inheritance; however, recessive and oligogenic models of transmission of cancer susceptibility also need to be considered. It is expected that the list of medically relevant tumor-predisposing genes will be rapidly expanding in the next few years.
authors.affiliation: Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg 194100, Russia.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sokolenko
authors.affiliation: Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg 194100, Russia.
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Suspitsin
authors.affiliation: Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.
authors.forename: Ekatherina Sh
authors.initials: ESh
authors.lastname: Kuligina
authors.affiliation: Laboratory of Bioinformatics, RASA Research Center, St.-Petersburg State Polytechnical University, St.-Petersburg 195251, Russia.
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Bizin
authors.affiliation: Department of Bioinformatics, Wissenschaftszentrum Weihenstephan, TU Muenchen, Freising 85354, Germany; Helmholtz Center Munich - German Research Center for Environmental Health (GmbH), Institute of Bioinformatics and Systems Biology, Neuherberg 85764, Germany.
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Frishman
authors.affiliation: Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg 194100, Russia; Department of Oncology, I.I. Mechnikov North-Western Medical University, St.-Petersburg 191015, Russia; Department of Oncology, St.-Petersburg State University, St.-Petersburg 199034, Russia. Electronic address: evgeny@imyanitov.spb.ru.
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D004198:Disease Susceptibility; D059472:Exome; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
keywords: Cancer susceptibility; Germ-line mutation; Hereditary cancer syndromes; Next generation sequencing; Whole exome sequencing