Whole-Genome Sequencing Reveals Elevated Tumor Mutational Burden and Initiating Driver Mutations in African Men with Treatment-Naïve, High-Risk Prostate Cancer

Cancer Research
Weerachai JaratlerdsiriVanessa M Hayes

Abstract

: African-American men are more likely than any other racial group to die from prostate cancer. The contribution of acquired genomic variation to this racial disparity is largely unknown, as genomic from Africa is lacking. Here, we performed the first tumor-normal paired deep whole-genome sequencing for Africa. A direct study-matched comparison between African- and European-derived, treatment-naïve, high-risk prostate tumors for 15 cases allowed for further comparative analyses of existing data. Excluding a single hypermutated tumor with 55 mutations per megabase, we observed a 1.8-fold increase in small somatic variants in African- versus European-derived tumors (P = 1.02e-04), rising to 4-fold when compared with published tumor-matched data. Furthermore, we observed an increase in oncogenic driver mutations in African tumors (P = 2.92e-03); roughly 30% of impacted genes were novel to prostate cancer, and 79% of recurrent driver mutations appeared early in tumorigenesis. Although complex genomic rearrangements were less frequent in African tumors, we describe a uniquely hyperduplicated tumor affecting 149 transposable elements. Comparable with African Americans, ERG fusions and PIK3CA mutations were absent and PTEN loss less f...Continue Reading

References

Jul 3, 2003·Nature Reviews. Molecular Cell Biology·Sten OrreniusPierluigi Nicotera
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 29, 2010·Cancer Cell·Barry S TaylorWilliam L Gerald
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Feb 11, 2011·Nature·Michael F BergerLevi A Garraway
Feb 1, 2012·Clinical Epidemiology·Michael F Leitzmann, Sabine Rohrmann
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
May 15, 2012·Bioinformatics·Christopher T SaundersR Keira Cheetham
Jan 15, 2013·Current Protocols in Human Genetics·Ivan AdzhubeiShamil R Sunyaev
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
Mar 22, 2013·PLoS Genetics·Desiree C PetersenVanessa M Hayes
Apr 30, 2013·Cell·Sylvan C BacaLevi A Garraway
Jul 23, 2013·PLoS Computational Biology·Umadevi PailaAaron R Quinlan
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Mar 22, 2014·BMC Bioinformatics·Shaylan K GovindPaul C Boutros
Apr 12, 2014·The Prostate·Elizabeth A TindallVanessa M Hayes
Jun 7, 2014·Molecular Cell·Hariharan EaswaranStephen B Baylin
Jun 28, 2014·Genome Biology·Ryan M LayerIra M Hall
Jul 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Haley HieronymusCharles L Sawyers
Sep 15, 2014·Nature Genetics·Ali Amin Al OlamaChristopher A Haiman
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray
Oct 17, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F FaveroA C Eklund
Feb 24, 2015·Human Mutation·Alex H RamosGad Getz
May 23, 2015·Cell·Dan RobinsonArul M Chinnaiyan
Jul 15, 2015·Bioinformatics·Julian S GehringWolfgang Huber
Aug 6, 2015·Cancer Causes & Control : CCC·Song-Yi ParkBrian E Henderson
Oct 3, 2015·Bioinformatics·Konstantin OkonechnikovFernando García-Alcalde
Nov 7, 2015·Cell·UNKNOWN Cancer Genome Atlas Research Network
Jan 10, 2016·JAMA : the Journal of the American Medical Association·Lorelei A MucciUNKNOWN Nordic Twin Study of Cancer (NorTwinCan) Collaboration
Feb 28, 2016·Cancer Research·Karla J LindquistJohn S Witte
Apr 23, 2016·PLoS Computational Biology·Eric TalevichBoris C Bastian
Jul 2, 2016·JAMA Oncology·Daniel E SprattJoseph R Osborne
Aug 18, 2016·The New England Journal of Medicine·Arjun K ManraiIsaac S Kohane
Dec 3, 2016·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Jan 10, 2017·Nature·Michael FraserPaul C Boutros
Apr 21, 2017·Oncotarget·Weerachai JaratlerdsiriVanessa M Hayes
May 19, 2017·Cancer Discovery·Franklin W HuangLevi A Garraway
Aug 25, 2017·Molecular Cancer Therapeutics·Aaron M GoodmanRazelle Kurzrock

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Citations

Jan 8, 2019·Oncotarget·Vanessa M HayesM S Riana Bornman
Sep 10, 2020·British Journal of Cancer·Valentina A ZavalaLaura Fejerman
Dec 12, 2019·Frontiers in Oncology·Matthew J Ryan, Rohit Bose
Mar 1, 2020·Prostate Cancer and Prostatic Diseases·Oliver SartorCelestia S Higano
Dec 16, 2018·Cancer Research·Franklin W Huang
Aug 8, 2019·Cancer Research·Jiekun Yang, Mazhar Adli
Jan 24, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Farzana A FaisalTamara L Lotan
Jan 28, 2021·Annual Review of Medicine·Jennifer A FreedmanSteven R Patierno
Jan 12, 2021·Frontiers in Oncology·Islam El JaddaouiHassan Ghazal
Jan 8, 2021·Frontiers in Oncology·Abeer A BahnassyAbdel-Rahman N Zekri
Mar 5, 2021·Frontiers in Oncology·Solomon O RotimiBodour Salhia
Apr 22, 2021·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Atike BahcivanBinnur Onal
Jun 3, 2021·Cancers·Alia AlbawardiTarek A Bismar
May 31, 2021·Cancer Letters·Jack FreelandAndrew S Goldstein
Aug 5, 2021·Cancer & Metabolism·Stefano CacciatoreLuiz F Zerbini
Aug 28, 2021·European Urology Oncology·Brandon A MahalKosj Yamoah

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