Abstract
The prevalence of homologous recombination DNA damage repair (HR-DDR) deficiencies among all tumor lineages is not well characterized. Therapy directed toward homologous recombination DDR deficiency (HRD) is now approved in ovarian and breast cancer, and there may be additional opportunities for benefit for patients with other cancers. Comprehensive evaluations for HRD are limited in part by the lack of a uniform, cost-effective method for testing and defining HRD. Molecular profiles of 52,426 tumors were reviewed to identify pathogenic mutations in the HR-DDR genes ARID1A, ATM, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CHEK1/2, FANCA/C/D2/E/F/G/L, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, or WRN. From solid tumors submitted to Caris Life Sciences, molecular profiles were generated using next-generation sequencing (NGS; average read depth, 500×). A total of 17,566 tumors were sequenced with NGS600 (n = 592 genes), and 34,860 tumors underwent hotspot Illumina MiSeq platform testing (n = 47 genes). Of the tumors that underwent NGS600 testing, the overall frequency of HRDDR mutations detected was 17.4%, and the most commonly mutated lineages were endometrial (34.4%; n = 1,475), biliary tract (28.9%; n = 343), bladder (23.9%; n = 201...Continue Reading
References
Apr 29, 1998·American Journal of Human Genetics·D FordM Zelada-Hedman
Aug 5, 1999·Journal of the National Cancer Institute·UNKNOWN Breast Cancer Linkage Consortium
Apr 5, 2003·American Journal of Human Genetics·A AntoniouD F Easton
Jul 29, 2004·British Journal of Cancer·S AngèleJ Hall
Sep 25, 2004·Genes, Chromosomes & Cancer·E CavaciutiN Andrieu
Aug 17, 2006·Cancer Research·Nuala McCabeAlan Ashworth
Aug 24, 2006·Nature Reviews. Molecular Cell Biology·Patrick Sung, Hannah Klein
Sep 26, 2006·Oncogene·A C Antoniou, D F Easton
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
Apr 10, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sining Chen, Giovanni Parmigiani
Oct 10, 2007·American Journal of Human Genetics·Douglas F EastonDavid E Goldgar
Nov 16, 2007·Genes & Development·Yiduo HuGuangbin Luo
Oct 16, 2008·Familial Cancer·Daniel H KimMary S Beattie
Dec 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cristina R FerroneMark E Robson
Mar 6, 2010·Breast Cancer Research and Treatment·Dorina M van der KolkJan C Oosterwijk
Jun 17, 2010·Cancer Research·Ponnari GottipatiThomas Helleday
Sep 9, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dorine RossettoJacques Côté
Feb 3, 2011·Cancer Research·Silvia CasadeiMary-Claire King
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Sep 29, 2011·British Journal of Cancer·Z Kote-JaraiR Eeles
Mar 29, 2012·The New England Journal of Medicine·Jonathan LedermannUrsula Matulonis
Apr 21, 2012·British Journal of Cancer·D LeongamornlertZ Kote-Jarai
May 16, 2012·Cancer Discovery·Nicholas J RobertsAlison P Klein
Oct 27, 2012·British Journal of Cancer·J IqbalUNKNOWN Hereditary Breast Cancer Study Group
Apr 9, 2013·Human Genomics·Robert C GrantSteven Gallinger
May 1, 2013·Journal of the National Cancer Institute·Nasim MavaddatUNKNOWN EMBRACE
Nov 19, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kathryn P PenningtonElizabeth M Swisher
Dec 7, 2013·Clinical Genetics·J M EggingtonR J Wenstrup
Dec 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Helen YuEl Bachir Affar
Jul 30, 2014·British Journal of Cancer·T GolanS Gallinger
Aug 8, 2014·The New England Journal of Medicine·Antonis C AntoniouMarc Tischkowitz
Oct 16, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kai Lee YapYusuke Nakamura
Nov 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bella KaufmanSusan M Domchek
Feb 13, 2015·Molecular Cancer Therapeutics·Marieke AartsNicholas C Turner
Mar 1, 2015·Gynecologic Oncology·Christine S Walsh
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Apr 10, 2015·Nature Communications·Agnieszka K WitkiewiczErik S Knudsen
Jun 13, 2015·Cancer Discovery·Jianfeng ShenGuang Peng
Aug 8, 2015·Breast Cancer Research and Treatment·Filipa LynceClaudine Isaacs
Aug 19, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yung-Jue BangWoo Ho Kim
Oct 29, 2015·The New England Journal of Medicine·Joaquin MateoJohann S de Bono
Jan 30, 2016·Oncotarget·Po-Han LinChiun-Sheng Huang
Mar 10, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Melinda L TelliAndrea L Richardson
Mar 27, 2016·Gynecologic Oncology·Marina FrimerJune Y Hou
Apr 3, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MoschettaS Banerjee
Jul 20, 2016·The New England Journal of Medicine·Colin C PritchardPeter S Nelson
Oct 9, 2016·The New England Journal of Medicine·Mansoor R MirzaUNKNOWN ENGOT-OV16/NOVA Investigators
Dec 3, 2016·The Lancet Oncology·Elizabeth M SwisherIain A McNeish
Dec 21, 2016·The Journal of Molecular Diagnostics : JMD·Marilyn M LiMarina N Nikiforova
Mar 1, 2017·Breast Cancer Research and Treatment·Naoko MatsudaNaoto T Ueno
Citations
Apr 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Raffit HassanJane E Churpek
Jun 7, 2019·Cancers·Roxane MariRenaud Sabatier
Jan 25, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eileen M O'ReillyDavid P Kelsen
May 2, 2019·The Oncologist·Aparna R ParikhAlexa B Schrock
Feb 8, 2020·Genes & Development·Dea Slade
Jul 2, 2020·Cancers·Kristyna TomasovaPavel Vodicka
Aug 11, 2020·Breast Cancer Research and Treatment·Arielle L HeekeAntoinette R Tan
Sep 1, 2020·Expert Review of Anticancer Therapy·Ritika Halder, Rachna T Shroff
Oct 31, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Roopa Thapar
Sep 11, 2019·Cancers·Violeta Bakardjieva-MihaylovaLudmila Boublikova
Jan 11, 2020·Frontiers in Oncology·Anika Trenner, Alessandro A Sartori
May 28, 2020·Frontiers in Oncology·Praveen VikasRohan Garje
Aug 18, 2020·Cancer Management and Research·Lucia MusacchioSandro Pignata
Sep 11, 2019·Cancers·Geetanjali SainiRitu Aneja
Jul 31, 2020·NPJ Breast Cancer·Sherko KuemmelMattea Reinisch
Sep 17, 2020·International Journal of Molecular Sciences·Samuele LodovichiAlvaro Galli
Sep 12, 2019·Pathology Oncology Research : POR·Philipp J SpachmannJohannes Breyer
May 28, 2020·Cancers·Kai ZimmerAndreas Seeber
Apr 20, 2020·Drugs·Ritu Raj Singh, Eileen M O'Reilly
Sep 3, 2020·International Journal of Molecular Sciences·Juan Carlos PardoAlbert Font
Jul 1, 2020·Current Treatment Options in Oncology·Satya Das, Dana Cardin
Apr 17, 2020·International Journal of Molecular Sciences·Saudade AndréCarmen Jerónimo
Mar 19, 2020·Journal of Ovarian Research·Jing NiXiaoxiang Chen
Sep 10, 2020·Methods and Protocols·Alice BradfieldDharani K Hapangama
Sep 4, 2020·Medicines·Angela Dalia RicciGiovanni Brandi
Nov 26, 2020·Cancers·Gulisa TurashviliJordan Lerner-Ellis
May 24, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wungki ParkEileen M O'Reilly
Nov 5, 2019·Molecular Cancer Therapeutics·Samantha A ArmstrongMichael J Pishvaian
Jan 10, 2021·Hereditary Cancer in Clinical Practice·Elżbieta Złowocka-PerłowskaJan Lubiński
Jan 17, 2021·Biomolecules·Nai-Jung ChiangMing-Huang Chen
Dec 17, 2020·Frontiers in Oncology·Ye HanCaigang Liu
Nov 21, 2020·Scientific Reports·Daniel R PrincipeAjay Rana
Mar 5, 2021·Expert Opinion on Investigational Drugs·Rutika MehtaRichard Kim
Feb 14, 2021·NPJ Breast Cancer·Sherko KuemmelMattea Reinisch
Apr 4, 2021·International Journal of Molecular Sciences·Margaret Ottaviano On Behalf Of Scito Youth
Apr 17, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Francesco SchettiniDaniele Generali
Apr 18, 2021·Genome Biology·Binsheng GongJoshua Xu
May 1, 2021·Cancers·Olga KondrashovaAmanda B Spurdle
Apr 19, 2021·Cancer Genetics·Yael LaitmanEitan Friedman
May 6, 2021·BMC Cancer·Nina LapkeShu-Jen Chen
Jun 3, 2021·Cancers·Sandra van WilpeNiven Mehra
Jun 3, 2021·Cancers·Masayuki SekineTakayuki Enomoto
Jun 20, 2021·NPJ Precision Oncology·Miklos DiossyZoltan Szallasi
Jun 22, 2021·Der Pathologe·N Pfarr, S Merkelbach-Bruse
Jul 3, 2021·Journal of Personalized Medicine·Svenja Wagener-RyczekJanna Siemanowski
Jul 3, 2021·Cancers·Sandy ChevrierRomain Boidot
Jul 3, 2021·Cancers·Kimberly M BurcherMercedes Porosnicu
Jul 3, 2021·Cancers·Paula Pellenz TomasiniJenifer Saffi
Jul 16, 2021·Curēus·Matthew I EbiaGino K In
Mar 8, 2021·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Hai-Yun WangFang Wang