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Mol Cell Proteomics DOI:10.1074/mcp.M115.056226

An Analysis of the Sensitivity of Proteogenomic Mapping of Somatic Mutations and Novel Splicing Events in Cancer.

Publication TypeJournal Article
Year of Publication2016
AuthorsRuggles, KV, Tang, Z, Wang, X, Grover, H, Askenazi, M, Teubl, J, Cao, S, McLellan, MD, Clauser, KR, Tabb, DL, Mertins, P, Slebos, R, Erdmann-Gilmore, P, Li, S, Gunawardena, HP, Xie, L, Liu, T, Zhou, J-Y, Sun, S, Hoadley, KA, Perou, CM, Chen, X, Davies, SR, Maher, CA, Kinsinger, CR, Rodland, KD, Zhang, H, Zhang, Z, Ding, L, R Townsend, R, Rodriguez, H, Chan, D, Smith, RD, Liebler, DC, Carr, SA, Payne, S, Ellis, MJ, Fenyö, D
JournalMol Cell Proteomics
Volume15
Issue3
Pages1060-71
Date Published2016 Mar
ISSN1535-9484
KeywordsAlternative Splicing, Animals, Computational Biology, Databases, Genetic, Female, Genome, Humans, Mammary Neoplasms, Experimental, Mice, Mutation, Polymorphism, Single Nucleotide, Proteomics, Sequence Analysis, DNA, Sequence Analysis, RNA, Tandem Mass Spectrometry, Transcriptome
Abstract

Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations, and splice variants identified in cancer cells are translated. Herein, we apply a proteogenomic data integration tool (QUILTS) to illustrate protein variant discovery using whole genome, whole transcriptome, and global proteome datasets generated from a pair of luminal and basal-like breast-cancer-patient-derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS sample process replicates defined here as an independent tandem MS experiment using identical sample material. Despite analysis of over 30 sample process replicates, only about 10% of SNVs (somatic and germline) detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (

URLhttp://www.mcponline.org/cgi/pmidlookup?view=long&pmid=26631509
DOI10.1074/mcp.M115.056226
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26631509?dopt=Abstract

Alternate JournalMol. Cell Proteomics
PubMed ID26631509
PubMed Central IDPMC4813688
Grant ListU24 CA160034 / CA / NCI NIH HHS / United States
U24 CA159988 / CA / NCI NIH HHS / United States
U24CA159988 / CA / NCI NIH HHS / United States
P50 CA058223 / CA / NCI NIH HHS / United States
U24CA160036 / CA / NCI NIH HHS / United States
U24 CA160036 / CA / NCI NIH HHS / United States
P30 CA091842 / CA / NCI NIH HHS / United States
U24 CA160019 / CA / NCI NIH HHS / United States
U24 CA160035 / CA / NCI NIH HHS / United States
U24CA160034 / CA / NCI NIH HHS / United States
U24CA160035 / CA / NCI NIH HHS / United States
U24CA160019 / CA / NCI NIH HHS / United States
T32 GM088118 / GM / NIGMS NIH HHS / United States