Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status

J. M. Cunningham; M. S. Cicek; N. B. Larson; J. Davila; C. Wang; M. C. Larson; H. Song; E. M. Dicks; P. Harrington; M. Wick; B. J. Winterhoff; H. Hamidi; G. E. Konecny; J. Chien; M. Bibikova; J. B. Fan; K. R. Kalli; N. M. Lindor; B. L. Fridley; P. P.D. Pharoah; E. L. Goode

doi:10.1038/srep04026

Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status

J. M. Cunningham, M. S. Cicek, N. B. Larson, J. Davila, C. Wang, M. C. Larson, H. Song, E. M. Dicks, P. Harrington, M. Wick, B. J. Winterhoff, H. Hamidi, G. E. Konecny, J. Chien, M. Bibikova, J. B. Fan, K. R. Kalli, N. M. Lindor, B. L. Fridley, P. P.D. PharoahE. L. Goode

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Abstract

We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.

Original language	English (US)
Article number	4026
Journal	Scientific reports
Volume	4
DOIs	https://doi.org/10.1038/srep04026
State	Published - Feb 7 2014

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Cunningham, J. M., Cicek, M. S., Larson, N. B., Davila, J., Wang, C., Larson, M. C., Song, H., Dicks, E. M., Harrington, P., Wick, M., Winterhoff, B. J., Hamidi, H., Konecny, G. E., Chien, J., Bibikova, M., Fan, J. B., Kalli, K. R., Lindor, N. M., Fridley, B. L., ... Goode, E. L. (2014). Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Scientific reports, 4, Article 4026. https://doi.org/10.1038/srep04026

Cunningham, JM , Cicek, MS , Larson, NB, Davila, J, Wang, C, Larson, MC, Song, H, Dicks, EM, Harrington, P, Wick, M, Winterhoff, BJ, Hamidi, H, Konecny, GE, Chien, J, Bibikova, M, Fan, JB, Kalli, KR, Lindor, NM, Fridley, BL, Pharoah, PPD & Goode, EL 2014, 'Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status', Scientific reports, vol. 4, 4026. https://doi.org/10.1038/srep04026

@article{1b321f36a0804efe89e7fbc70cffe8e4,

title = "Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status",

abstract = "We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.",

author = "Cunningham, {J. M.} and Cicek, {M. S.} and Larson, {N. B.} and J. Davila and C. Wang and Larson, {M. C.} and H. Song and Dicks, {E. M.} and P. Harrington and M. Wick and Winterhoff, {B. J.} and H. Hamidi and Konecny, {G. E.} and J. Chien and M. Bibikova and Fan, {J. B.} and Kalli, {K. R.} and Lindor, {N. M.} and Fridley, {B. L.} and Pharoah, {P. P.D.} and Goode, {E. L.}",

note = "Funding Information: This work was supported by National Institutes of Health grants R01-CA122443, P50-CA136393, P30-CA15083, and the Fred C. and Katherine B. Andersen Foundation. We thank Gary Kenney, M.D. for pathology review of tumor tissue. We thank Craig Luccarini, Caroline Baynes from University of Cambridge for assisting our sample sequencing.",

year = "2014",

month = feb,

day = "7",

doi = "10.1038/srep04026",

language = "English (US)",

volume = "4",

journal = "Scientific reports",

issn = "2045-2322",

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TY - JOUR

T1 - Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status

AU - Cunningham, J. M.

AU - Cicek, M. S.

AU - Larson, N. B.

AU - Davila, J.

AU - Wang, C.

AU - Larson, M. C.

AU - Song, H.

AU - Dicks, E. M.

AU - Harrington, P.

AU - Wick, M.

AU - Winterhoff, B. J.

AU - Hamidi, H.

AU - Konecny, G. E.

AU - Chien, J.

AU - Bibikova, M.

AU - Fan, J. B.

AU - Kalli, K. R.

AU - Lindor, N. M.

AU - Fridley, B. L.

AU - Pharoah, P. P.D.

AU - Goode, E. L.

N1 - Funding Information: This work was supported by National Institutes of Health grants R01-CA122443, P50-CA136393, P30-CA15083, and the Fred C. and Katherine B. Andersen Foundation. We thank Gary Kenney, M.D. for pathology review of tumor tissue. We thank Craig Luccarini, Caroline Baynes from University of Cambridge for assisting our sample sequencing.

PY - 2014/2/7

Y1 - 2014/2/7

N2 - We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.

AB - We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.

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U2 - 10.1038/srep04026

DO - 10.1038/srep04026

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SN - 2045-2322

VL - 4

JO - Scientific reports

JF - Scientific reports

M1 - 4026

ER -

Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status

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