High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers

Annals of Oncology : Official Journal of the European Society for Medical Oncology
Elena CastroUKGPCS, EMBRACE and IMPACT studies

Abstract

Germline BRCA2 mutations are associated with poorer outcome prostate cancer (PCa) compared with sporadic tumours but this association remains to be characterised. In this study, we aim to assess if there is a signature set of copy number alterations (CNA) that could aid to the identification of BRCA2-mutated tumours and would assist us to understand their aggressive clinical behaviour. High-resolution array comparative genomic hybridisation profiling of DNA from PCa and matched morphologically normal prostate samples from 9 BRCA2 germline mutation carriers and 16 non-carriers in combination with unsupervised analysis was used to define copy number features. PCa from BRCA2 germline mutation carriers (B2T) harbour significantly more CNA than non-carrier tumours (NCTs) (P = 14 × 10(-6)). A hundred and sixteen regions had a significantly different distribution with both false discovery rate (FDR) and P value <0.01, including CNA in the genomic region containing c-MYC that was present in 89% B2T versus 12.5% NCT (P = 3 × 10(-4)). Loss of heterozygosity (LOH) at the BRCA2 locus was observed in 67% of B2T. Elevated CNA are already present in 50% of the morphologically normal prostate tissue from BRCA2 carriers. The relative high amoun...Continue Reading

References

Aug 5, 1999·Journal of the National Cancer Institute·UNKNOWN Breast Cancer Linkage Consortium
Feb 8, 2002·Cell·Ashok R Venkitaraman
Oct 29, 2004·Nature Reviews. Cancer·Nicholas TurnerAlan Ashworth
May 10, 2005·Bioinformatics·Mark A van de WielBauke Ylstra
Jan 20, 2007·Bioinformatics·E S Venkatraman, Adam B Olshen
Feb 3, 2007·Bioinformatics·Mark A van de WielBauke Ylstra
Jun 15, 2007·Journal of the National Cancer Institute·Laufey TryggvadóttirHrafn Tulinius
May 1, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amber J WillemsUNKNOWN kConFab Investigators
Jun 26, 2008·British Journal of Cancer·S A NarodChristina Bellati
Sep 11, 2008·The Prostate·Masayuki KobayashiTomohiko Ichikawa
Oct 29, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David S P TanMartin E Gore
Mar 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David J GallagherKenneth Offit
Jun 16, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Panagiotis A KonstantinopoulosStephen A Cannistra
Aug 26, 2010·British Journal of Cancer·S M EdwardsUNKNOWN UK Genetic Prostate Cancer Study Collaborators and BAUS Section of Oncology
May 10, 2012·The American Journal of Pathology·Yan P YuJian-Hua Luo
Jun 23, 2012·Nature·Catherine S GrassoScott A Tomlins
Apr 10, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elena CastroRosalind Eeles
Apr 30, 2013·Cell·Sylvan C BacaLevi A Garraway
Jul 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Haley HieronymusCharles L Sawyers
Oct 30, 2014·The New England Journal of Medicine·Donal P McLornanGhulam J Mufti

❮ Previous
Next ❯

Citations

Oct 30, 2016·European Urology·Joaquin MateoJohann S de Bono
Aug 5, 2016·PLoS Genetics·Suzanne A HartfordShyam K Sharan
Jan 10, 2017·Nature Communications·Renea A TaylorRobert G Bristow
Jul 1, 2017·Current Opinion in Urology·Joachim Weischenfeldt, Jan O Korbel
Nov 5, 2017·Cold Spring Harbor Perspectives in Medicine·Alexander DiasRos Eeles
Jan 10, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elena CastroDavid Olmos
Sep 25, 2019·Cancer Immunology, Immunotherapy : CII·Maximilian JenzerStefan Duensing
Jul 6, 2017·Scientific Reports·Cathleen NientiedtStefan Duensing
Feb 28, 2019·Nature Reviews. Urology·Renea A TaylorGail P Risbridger
Jun 22, 2017·Molecular Cancer Research : MCR·Silvia MaifredeTomasz Skorski
Feb 19, 2019·Asian Journal of Urology·William B Isaacs, Jianfeng Xu
Feb 25, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Rebeca LozanoElena Castro
May 1, 2021·International Journal of Molecular Sciences·Maria Teresa VietriAnna Maria Molinari
Apr 30, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N Romero-LaordenD Olmos

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.