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

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Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication. / Pelttari, L. M.; Shimelis, H.; Toiminen, H.; Kvist, A.; Törngren, T.; Borg, A.; Blomqvist, C.; Bützow, R.; Couch, F.; Aittomäki, K.; Nevanlinna, H.

I: Clinical Genetics, Vol. 93, Nr. 3, 2018, s. 595-602.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Pelttari, LM, Shimelis, H, Toiminen, H, Kvist, A, Törngren, T, Borg, A, 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, nr. 3, s. 595-602. https://doi.org/10.1111/cge.13123

APA

Pelttari, L. M., Shimelis, H., Toiminen, H., Kvist, A., Törngren, T., Borg, A., 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, 93(3), 595-602. https://doi.org/10.1111/cge.13123

CBE

Pelttari LM, Shimelis H, Toiminen H, Kvist A, Törngren T, Borg A, 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. 93(3):595-602. https://doi.org/10.1111/cge.13123

MLA

Vancouver

Author

Pelttari, L. M. ; Shimelis, H. ; Toiminen, H. ; Kvist, A. ; Törngren, T. ; Borg, A. ; Blomqvist, C. ; Bützow, R. ; Couch, F. ; Aittomäki, K. ; Nevanlinna, H. / Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication. I: Clinical Genetics. 2018 ; Vol. 93, Nr. 3. s. 595-602.

RIS

TY - JOUR

T1 - Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication

AU - Pelttari, L. M.

AU - Shimelis, H.

AU - Toiminen, H.

AU - Kvist, A.

AU - Törngren, T.

AU - Borg, A.

AU - Blomqvist, C.

AU - Bützow, R.

AU - Couch, F.

AU - Aittomäki, K.

AU - Nevanlinna, H.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Gene-panel

KW - Ovarian cancer

KW - RAD51C

UR - http://www.scopus.com/inward/record.url?scp=85040679080&partnerID=8YFLogxK

U2 - 10.1111/cge.13123

DO - 10.1111/cge.13123

M3 - Article

C2 - 28802053

AN - SCOPUS:85040679080

VL - 93

SP - 595

EP - 602

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 3

ER -