Search: WFRF:(Thompson Alastair M.)
> (2015-2019) >
HRDetect is a predi...
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
-
- Davies, Helen R. (author)
- Wellcome Trust Sanger Institute
-
- Glodzik, Dominik (author)
- Wellcome Trust Sanger Institute
-
- Morganella, Sandro (author)
- Wellcome Trust Sanger Institute
-
show more...
-
- Yates, Lucy R. (author)
- Guy's and St Thomas' NHS Foundation Trust
-
- Staaf, Johan (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
-
- Zou, Xueqing (author)
- Wellcome Trust Sanger Institute
-
- Ramakrishna, Manasa (author)
- AstraZeneca, UK
-
- Martin, Sancha (author)
- Wellcome Trust Sanger Institute
-
- Boyault, Sandrine (author)
- Centre Léon Bérard
-
- Sieuwerts, Anieta M. (author)
- Erasmus University Rotterdam
-
- Simpson, Peter T (author)
- University of Queensland
-
- King, Tari A (author)
- Memorial Sloan-Kettering Cancer Center
-
- Raine, Keiran (author)
- Wellcome Trust Sanger Institute
-
- Eyfjord, Jorunn E. (author)
- University of Iceland
-
- Kong, Gu (author)
- Hanyang University
-
- Borg, Åke (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups
-
- Birney, Ewan (author)
- European Bioinformatics Institute
-
- Stunnenberg, Hendrik G. (author)
- Radboud University Nijmegen
-
- van de Vijver, Marc J (author)
- Academic Medical Center of University of Amsterdam (AMC)
-
- Børresen-Dale, Anne-Lise (author)
- University of Oslo
-
- Martens, John W. M. (author)
- Erasmus University Rotterdam
-
- Span, Paul N. (author)
- Radboud University Medical Center
-
- Lakhani, Sunil R. (author)
- Royal Brisbane and Women's Hospital
-
- Vincent-Salomon, Anne (author)
- Curie Institute, Paris
-
- Sotiriou, Christos (author)
- Université Libre de Bruxelles (ULB)
-
- Tutt, Andrew (author)
- Institute of Cancer Research London
-
- Thompson, Alastair M (author)
- University of Texas
-
- Van Laere, Steven (author)
- HistoGeneX NV
-
- Richardson, Andrea L. (author)
- Dana-Farber Cancer Institute
-
- Viari, Alain (author)
- Centre Léon Bérard
-
- Campbell, Peter J. (author)
- Wellcome Trust Sanger Institute
-
- Stratton, Michael R. (author)
- Wellcome Trust Sanger Institute
-
- Nik-Zainal, Serena (author)
- Cambridge University Hospitals NHS Foundation Trust
-
show less...
-
(creator_code:org_t)
- 2017-03-13
- 2017
- English 9 s.
-
In: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 23:4, s. 517-525
- Related links:
-
http://dx.doi.org/10...
-
show more...
-
https://europepmc.or...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database
- By the author/editor
-
Davies, Helen R.
-
Glodzik, Dominik
-
Morganella, Sand ...
-
Yates, Lucy R.
-
Staaf, Johan
-
Zou, Xueqing
-
show more...
-
Ramakrishna, Man ...
-
Martin, Sancha
-
Boyault, Sandrin ...
-
Sieuwerts, Aniet ...
-
Simpson, Peter T
-
King, Tari A
-
Raine, Keiran
-
Eyfjord, Jorunn ...
-
Kong, Gu
-
Borg, Åke
-
Birney, Ewan
-
Stunnenberg, Hen ...
-
van de Vijver, M ...
-
Børresen-Dale, A ...
-
Martens, John W. ...
-
Span, Paul N.
-
Lakhani, Sunil R ...
-
Vincent-Salomon, ...
-
Sotiriou, Christ ...
-
Tutt, Andrew
-
Thompson, Alasta ...
-
Van Laere, Steve ...
-
Richardson, Andr ...
-
Viari, Alain
-
Campbell, Peter ...
-
Stratton, Michae ...
-
Nik-Zainal, Sere ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
- Articles in the publication
-
Nature Medicine
- By the university
-
Lund University