Your browser doesn't support javascript.
loading
Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.
Pritchard, Colin C; Mateo, Joaquin; Walsh, Michael F; De Sarkar, Navonil; Abida, Wassim; Beltran, Himisha; Garofalo, Andrea; Gulati, Roman; Carreira, Suzanne; Eeles, Rosalind; Elemento, Olivier; Rubin, Mark A; Robinson, Dan; Lonigro, Robert; Hussain, Maha; Chinnaiyan, Arul; Vinson, Jake; Filipenko, Julie; Garraway, Levi; Taplin, Mary-Ellen; AlDubayan, Saud; Han, G Celine; Beightol, Mallory; Morrissey, Colm; Nghiem, Belinda; Cheng, Heather H; Montgomery, Bruce; Walsh, Tom; Casadei, Silvia; Berger, Michael; Zhang, Liying; Zehir, Ahmet; Vijai, Joseph; Scher, Howard I; Sawyers, Charles; Schultz, Nikolaus; Kantoff, Philip W; Solit, David; Robson, Mark; Van Allen, Eliezer M; Offit, Kenneth; de Bono, Johann; Nelson, Peter S.
Affiliation
  • Pritchard CC; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Mateo J; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Walsh MF; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • De Sarkar N; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Abida W; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Beltran H; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Garofalo A; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Gulati R; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Carreira S; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Eeles R; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Elemento O; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Rubin MA; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Robinson D; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Lonigro R; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Hussain M; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Chinnaiyan A; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Vinson J; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Filipenko J; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Garraway L; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Taplin ME; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • AlDubayan S; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Han GC; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Beightol M; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Morrissey C; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Nghiem B; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Cheng HH; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Montgomery B; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Walsh T; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Casadei S; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Berger M; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Zhang L; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Zehir A; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Vijai J; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Scher HI; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Sawyers C; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Schultz N; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Kantoff PW; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Solit D; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Robson M; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Van Allen EM; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Offit K; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • de Bono J; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
  • Nelson PS; From the University of Washington (C.C.P., M. Beightol, C.M., B.N., H.H.C., B.M., T.W., S. Casadei, P.S.N.) and Fred Hutchinson Cancer Research Center (N.D.S., R.G., P.S.N.) - both in Seattle; the Institute of Cancer Research and Royal Marsden Hospital, London (J.M., S. Carreira, R.E., J.B.); Memori
N Engl J Med ; 375(5): 443-53, 2016 Aug 04.
Article in En | MEDLINE | ID: mdl-27433846
ABSTRACT

BACKGROUND:

Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established.

METHODS:

We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes.

RESULTS:

A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001).

CONCLUSIONS:

In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer. (Funded by Stand Up To Cancer and others.).
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms / Germ-Line Mutation / DNA Repair Type of study: Clinical_trials / Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Humans / Male / Middle aged Language: En Journal: N Engl J Med Year: 2016 Document type: Article
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms / Germ-Line Mutation / DNA Repair Type of study: Clinical_trials / Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Humans / Male / Middle aged Language: En Journal: N Engl J Med Year: 2016 Document type: Article