Linking Binary Gene Relationships to Drivers of Renal Cell Carcinoma Reveals Convergent Function in Alternate Tumor Progression Paths

Scientific Reports
William L PoehlmanF Alex Feltus

Abstract

Renal cell carcinoma (RCC) subtypes are characterized by distinct molecular profiles. Using RNA expression profiles from 1,009 RCC samples, we constructed a condition-annotated gene coexpression network (GCN). The RCC GCN contains binary gene coexpression relationships (edges) specific to conditions including RCC subtype and tumor stage. As an application of this resource, we discovered RCC GCN edges and modules that were associated with genetic lesions in known RCC driver genes, including VHL, a common initiating clear cell RCC (ccRCC) genetic lesion, and PBRM1 and BAP1 which are early genetic lesions in the Braided Cancer River Model (BCRM). Since ccRCC tumors with PBRM1 mutations respond to targeted therapy differently than tumors with BAP1 mutations, we focused on ccRCC-specific edges associated with tumors that exhibit alternate mutation profiles: VHL-PBRM1 or VHL-BAP1. We found specific blends molecular functions associated with these two mutation paths. Despite these mutation-associated edges having unique genes, they were enriched for the same immunological functions suggesting a convergent functional role for alternate gene sets consistent with the BCRM. The condition annotated RCC GCN described herein is a novel data ...Continue Reading

References

May 24, 2001·Proceedings of the National Academy of Sciences of the United States of America·I HellstromK E Hellstrom
Apr 9, 2002·Experimental Nephrology·Jamie A Davies, Carolyn E Fisher
Nov 25, 2003·The Journal of Urology·W Marston LinehanBerton Zbar
Jul 7, 2007·Cancer Cell·David A Guertin, David M Sabatini
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Mar 6, 2010·Immunology·John S YiAllan J Zajac
Jun 22, 2010·Nature·Yong-Yeol AhnSune Lehmann
Jan 5, 2011·Cancer Research·Miao-Chih TsaiHoward Y Chang
Jul 9, 2011·Nature Immunology·E John Wherry
Apr 9, 2013·PloS One·Lina-Marcela Diaz-GalloJavier Martin
Apr 25, 2013·Bioinformatics·Sriganesh Srihari, Mark A Ragan
Jun 25, 2013·Nature·UNKNOWN Cancer Genome Atlas Research Network
Sep 28, 2013·Nature Genetics·UNKNOWN Cancer Genome Atlas Research NetworkJoshua M Stuart
Nov 3, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephen J BlakeMark J Smyth
Oct 22, 2016·Clinical and Translational Medicine·James J Hsieh, Emily H Cheng
Mar 5, 2017·Immunological Reviews·Lawrence P AndrewsDario A A Vignali
Mar 5, 2017·Immunological Reviews·William C DougallAna C Anderson
Mar 10, 2017·Nature Reviews. Disease Primers·James J HsiehVincenzo Ficarra
Dec 24, 2017·Journal of Cellular Biochemistry·Jin-Cheng WangXiao-Jie Lu
Mar 16, 2018·Oncotarget·Leland J DunwoodieFrank Alexander Feltus
Mar 16, 2018·Cancer Immunology, Immunotherapy : CII·Francesca Finotello, Zlatko Trajanoski
Apr 5, 2018·Cell Reports·Christopher J RickettsW Marston Linehan
Apr 17, 2018·Cell·Samra TurajlicUNKNOWN TRACERx Renal Consortium
Aug 5, 2018·Journal of Cellular Physiology·Alexander Y Tsygankov

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Citations

Nov 19, 2019·Frontiers in Plant Science·William L PoehlmanFrank Alex Feltus
Mar 23, 2021·Frontiers in Big Data·Cameron OgleSusmit Shannigrahi

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Methods Mentioned

BETA
genotyping
RNAseq

Software Mentioned

analyzeNetCat
KINC
preprocessCore R
Cluster
R
HDBSCAN
_ Ensembles Python library
linkcomm R package
CentOS7
GDC Data Transfer Tool

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