Genomic features of renal cell carcinoma with venous tumor thrombus

Scientific Reports
Gregor WarsowStefan Duensing

Abstract

A venous tumor thrombus (VTT) is a potentially lethal complication of renal cell carcinoma (RCC) but virtually nothing is known about the underlying natural history. Based on our observation that venous thrombi contain significant numbers of viable tumor cells, we applied multiregion whole exome sequencing to a total of 37 primary tumor and VTT samples including normal tissue specimens from five consecutive patients. Our findings demonstrate mutational heterogeneity between primary tumor and VTT with 106 of 483 genes (22%) harboring functional SNVs and/or indels altered in either primary tumor or thrombus. Reconstruction of the clonal phylogeny showed clustering of tumor samples and VTT samples, respectively, in the majority of tumors. However, no new subclones were detected suggesting that pre-existing subclones of the primary tumor drive VTT formation. Importantly, we found several lines of evidence for "BRCAness" in a subset of tumors. These included mutations in genes that confer "BRCAness", a mutational signature and an increase of small indels. Re-analysis of SNV calls from the TCGA KIRC-US cohort confirmed a high frequency of the "BRCAness" mutational signature AC3 in clear cell RCC. Our findings warrant further pre-clin...Continue Reading

References

Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Mar 10, 2001·Molecular Cell·M E MoynahanM Jasin
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·F XiaS N Powell
Apr 18, 2007·The Journal of Urology·Axel HaferkampMarkus Hohenfellner
Jun 6, 2007·European Urology·Ziya Kirkali, Hein Van Poppel
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Jul 21, 2010·The Journal of Urology·Frédéric PouliotArie S Belldegrun
Jun 15, 2011·Bioinformatics·Adam B OlshenVenkatraman E Seshan
Jan 13, 2012·Urologic Oncology·Adam C ReeseMaxwell V Meng
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
Jul 27, 2012·Nature·David T W JonesPeter Lichter
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Jun 25, 2013·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jul 3, 2013·Nature Genetics·David T W JonesUNKNOWN International Cancer Genome Consortium PedBrain Tumor Project
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Jan 23, 2014·Cancer Research·Vanessa AlmendroKornelia Polyak
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Francesco GattoJens Nielsen
Apr 1, 2014·Current Urology Reports·Juan I Martínez-SalamancaJohn A Libertino
Nov 18, 2014·Nature Genetics·Steffen DurinckSomasekar Seshagiri
Oct 9, 2015·Therapeutic Advances in Urology·Sarah P Psutka, Bradley C Leibovich
Nov 5, 2015·The New England Journal of Medicine·W Marston LinehanUNKNOWN Cancer Genome Atlas Research Network
Nov 10, 2015·Nature Genetics·Ludmil B AlexandrovMichael R Stratton
Jan 19, 2016·Nature Reviews. Cancer·Christopher J Lord, Alan Ashworth
Apr 23, 2016·PLoS Computational Biology·Eric TalevichBoris C Bastian
Aug 31, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yuchao JiangNancy R Zhang
Mar 18, 2017·Science·Christopher J Lord, Alan Ashworth

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Datasets Mentioned

BETA
00001001950

Methods Mentioned

BETA
exome sequencing
deamination

Software Mentioned

YAPSA – Yet Another Package for Signature Analysis
R package Canopy
ACEseq
R package lsei
Canopy
mem
Platypus callVariants
R package SomaticSignatures
cnvKit
bwa

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