Proteogenomic characterization of human colon and rectal cancer

被引：1112

作者：

Zhang, Bing ^{[1
,2
]}

Wang, Jing ^{[1
]}

Wang, Xiaojing ^{[1
]}

Zhu, Jing ^{[1
]}

Liu, Qi ^{[1
]}

Shi, Zhiao ^{[3
,4
]}

Chambers, Matthew C. ^{[1
]}

Zimmerman, Lisa J. ^{[5
,6
]}

Shaddox, Kent F. ^{[6
]}

Kim, Sangtae ^{[7
]}

Davies, Sherri R. ^{[8
]}

Wang, Sean ^{[9
]}

Wang, Pei ^{[10
]}

Kinsinger, Christopher R. ^{[11
]}

Rivers, Robert C. ^{[11
]}

Rodriguez, Henry ^{[11
]}

Townsend, R. Reid ^{[8
]}

Ellis, Matthew J. C. ^{[8
]}

Carr, Steven A. ^{[12
]}

Tabb, David L. ^{[1
]}

Coffey, Robert J. ^{[13
]}

Slebos, Robbert J. C. ^{[2
,6
]}

Liebler, Daniel C. ^{[5
,6
]}

机构：

[1] Vanderbilt Univ Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA

[2] Vanderbilt Univ Sch Med, Dept Canc Biol, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Adv Comp Ctr Res & Educ, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Dept Elect Engn & Comp Sci, Nashville, TN 37232 USA

[5] Vanderbilt Univ Sch Med, Dept Biochem, Nashville, TN 37232 USA

[6] Vanderbilt Ingram Canc Ctr, Jim Ayers Inst Precanc Detect & Diag, Nashville, TN 37232 USA

[7] Pacific NW Natl Lab, Directorate Fundamental & Computat Sci, Richland, WA 99352 USA

[8] Washington Univ Sch Med, Dept Internal Med, St Louis, MO 63110 USA

[9] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[10] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

[11] NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA

[12] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[13] Vanderbilt Univ Sch Med, Dept Med, Nashville, TN 37232 USA

来源：

NATURE | 2014年 / 513卷 / 7518期

基金：

美国国家卫生研究院;

关键词：

RNA-SEQ DATA; PROTEIN EXPRESSION; COLORECTAL-CANCER; PEPTIDE IDENTIFICATION; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; ANALYSIS REVEALS; GENE; ABUNDANCE; HNF4-ALPHA;

D O I：

10.1038/nature13438

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenotype' transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A(hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology.

引用

页码：382 / +

页数：21

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