Advanced

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

Pelttari, L. M.; Shimelis, H.; Toiminen, H.; Kvist, A. LU ; Törngren, T. LU ; Borg, A. LU ; Blomqvist, C.; Bützow, R.; Couch, F. and Aittomäki, K., et al. (2018) In Clinical Genetics
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Breast cancer, Gene-panel, Ovarian cancer, RAD51C
in
Clinical Genetics
publisher
Wiley-Blackwell
external identifiers
  • scopus:85040679080
  • pmid:28802053
ISSN
0009-9163
DOI
language
English
LU publication?
yes
id
67504f2b-72f0-444f-bebe-3bcddcf312e6
date added to LUP
2018-02-05 13:06:54
date last changed
2018-05-29 11:32:25
@article{67504f2b-72f0-444f-bebe-3bcddcf312e6,
  abstract     = {<p>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.</p>},
  author       = {Pelttari, L. M. and Shimelis, H. and Toiminen, H. and Kvist, A. and Törngren, T. and Borg, A. and Blomqvist, C. and Bützow, R. and Couch, F. and Aittomäki, K. and Nevanlinna, H.},
  issn         = {0009-9163},
  keyword      = {Breast cancer,Gene-panel,Ovarian cancer,RAD51C},
  language     = {eng},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical Genetics},
  title        = {Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication},
  url          = {http://dx.doi.org/},
  year         = {2018},
}