Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication

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Pelttari , L M , Shimelis , H , Toiminen , H , Kvist , A , Törngren , T , Borg , Å , Blomqvist , C , Bützow , R , Couch , F , Aittomäki , K & Nevanlinna , H 2018 , ' Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication ' , Clinical Genetics , vol. 93 , no. 3 , pp. 595-602 . https://doi.org/10.1111/cge.13123

Title: Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication
Author: Pelttari, L. M.; Shimelis, H.; Toiminen, H.; Kvist, A.; Törngren, T.; Borg, Å.; Blomqvist, C.; Bützow, R.; Couch, F.; Aittomäki, K.; Nevanlinna, H.
Other contributor: University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, HUSLAB
University of Helsinki, Department of Oncology
University of Helsinki, Department of Pathology
University of Helsinki, Kristiina Aittomäki / Principal Investigator
University of Helsinki, Department of Obstetrics and Gynecology









Date: 2018-03
Language: eng
Number of pages: 8
Belongs to series: Clinical Genetics
ISSN: 0009-9163
DOI: https://doi.org/10.1111/cge.13123
URI: http://hdl.handle.net/10138/233854
Abstract: Gene-panel sequencing allows comprehensive analysis of multiple genes simultaneously and is now routinely used in clinical mutation testing of high-risk breast and ovarian cancer patients. However, only BRCA1 and BRCA2 are often analyzed also for large genomic changes. Here, we have analyzed 10 clinically relevant susceptibility genes in 95 breast or ovarian cancer patients with gene-panel sequencing including also copy number variants (CNV) analysis for genomic changes. We identified 12 different pathogenic BRCA1, BRCA2, TP53, PTEN, CHEK2, or RAD51C mutations in 18 of 95 patients (19%). BRCA1/2 mutations were observed in 8 patients (8.4%) and CHEK2 protein-truncating mutations in 7 patients (7.4%). In addition, we identified a novel duplication encompassing most of the RAD51C gene. We further genotyped the duplication in breast or ovarian cancer families (n=1149), in unselected breast (n=1729) and ovarian cancer cohorts (n=553), and in population controls (n=1273). Seven additional duplication carries were observed among cases but none among controls. The duplication associated with ovarian cancer risk (3/590 of all ovarian cancer patients, 0.5%, P=.032 compared with controls) and was found to represent a large fraction of all identified RAD51C mutations in the Finnish population. Our data emphasizes the importance of comprehensive mutation analysis including CNV detection in all the relevant genes.
Subject: breast cancer
gene-panel
ovarian cancer
RAD51C
CONFER SUSCEPTIBILITY
GERMLINE MUTATIONS
RISK
BRCA1
CHEK2-ASTERISK-1100DELC
POPULATION
COMPLEXES
PATTERNS
FAMILIES
PARALOGS
3111 Biomedicine
1184 Genetics, developmental biology, physiology
3123 Gynaecology and paediatrics
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