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Proteogenomic characterization of human colon and rectal cancer

Author

Listed:
  • Bing Zhang

    (Vanderbilt University School of Medicine
    Vanderbilt University School of Medicine)

  • Jing Wang

    (Vanderbilt University School of Medicine)

  • Xiaojing Wang

    (Vanderbilt University School of Medicine)

  • Jing Zhu

    (Vanderbilt University School of Medicine)

  • Qi Liu

    (Vanderbilt University School of Medicine)

  • Zhiao Shi

    (Advanced Computing Center for Research and Education, Vanderbilt University
    Vanderbilt University)

  • Matthew C. Chambers

    (Vanderbilt University School of Medicine)

  • Lisa J. Zimmerman

    (Vanderbilt University School of Medicine
    Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center)

  • Kent F. Shaddox

    (Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center)

  • Sangtae Kim

    (Directorate of Fundamental and Computational Sciences, Pacific Northwest National Laboratory)

  • Sherri R. Davies

    (Washington University School of Medicine)

  • Sean Wang

    (Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M2-B500, Seattle, Washington 98109, USA)

  • Pei Wang

    (Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1498, New York, New York 10029, USA)

  • Christopher R. Kinsinger

    (Office of Cancer Clinical Proteomics Research, National Cancer Institute)

  • Robert C. Rivers

    (Office of Cancer Clinical Proteomics Research, National Cancer Institute)

  • Henry Rodriguez

    (Office of Cancer Clinical Proteomics Research, National Cancer Institute)

  • R. Reid Townsend

    (Washington University School of Medicine)

  • Matthew J. C. Ellis

    (Washington University School of Medicine)

  • Steven A. Carr

    (Broad Institute of MIT and Harvard)

  • David L. Tabb

    (Vanderbilt University School of Medicine)

  • Robert J. Coffey

    (Vanderbilt University School of Medicine)

  • Robbert J. C. Slebos

    (Vanderbilt University School of Medicine
    Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center)

  • Daniel C. Liebler

    (Vanderbilt University School of Medicine
    Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center)

Abstract

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.

Suggested Citation

  • Bing Zhang & Jing Wang & Xiaojing Wang & Jing Zhu & Qi Liu & Zhiao Shi & Matthew C. Chambers & Lisa J. Zimmerman & Kent F. Shaddox & Sangtae Kim & Sherri R. Davies & Sean Wang & Pei Wang & Christopher, 2014. "Proteogenomic characterization of human colon and rectal cancer," Nature, Nature, vol. 513(7518), pages 382-387, September.
  • Handle: RePEc:nat:nature:v:513:y:2014:i:7518:d:10.1038_nature13438
    DOI: 10.1038/nature13438
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    Citations

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    Cited by:

    1. Angela Re & Levi Waldron & Alessandro Quattrone, 2016. "Control of Gene Expression by RNA Binding Protein Action on Alternative Translation Initiation Sites," PLOS Computational Biology, Public Library of Science, vol. 12(12), pages 1-25, December.
    2. S. Vickovic & B. Lötstedt & J. Klughammer & S. Mages & Å Segerstolpe & O. Rozenblatt-Rosen & A. Regev, 2022. "SM-Omics is an automated platform for high-throughput spatial multi-omics," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Sahar Harati & Lee A D Cooper & Josue D Moran & Felipe O Giuste & Yuhong Du & Andrei A Ivanov & Margaret A Johns & Fadlo R Khuri & Haian Fu & Carlos S Moreno, 2017. "MEDICI: Mining Essentiality Data to Identify Critical Interactions for Cancer Drug Target Discovery and Development," PLOS ONE, Public Library of Science, vol. 12(1), pages 1-18, January.
    4. Hailiang Zhang & Lin Bai & Xin-Qiang Wu & Xi Tian & Jinwen Feng & Xiaohui Wu & Guo-Hai Shi & Xiaoru Pei & Jiacheng Lyu & Guojian Yang & Yang Liu & Wenhao Xu & Aihetaimujiang Anwaier & Yu Zhu & Da-Long, 2023. "Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    5. Yan Li & Bing Wang & Wentao Yang & Fahan Ma & Jianling Zou & Kai Li & Subei Tan & Jinwen Feng & Yunzhi Wang & Zhaoyu Qin & Zhiyu Chen & Chen Ding, 2024. "Longitudinal plasma proteome profiling reveals the diversity of biomarkers for diagnosis and cetuximab therapy response of colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Paul A Stewart & Katja Parapatics & Eric A Welsh & André C Müller & Haoyun Cao & Bin Fang & John M Koomen & Steven A Eschrich & Keiryn L Bennett & Eric B Haura, 2015. "A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-18, November.
    7. Qi Liu & Charles A Herring & Quanhu Sheng & Jie Ping & Alan J Simmons & Bob Chen & Amrita Banerjee & Wei Li & Guoqiang Gu & Robert J Coffey & Yu Shyr & Ken S Lau, 2018. "Quantitative assessment of cell population diversity in single-cell landscapes," PLOS Biology, Public Library of Science, vol. 16(10), pages 1-29, October.
    8. Yiqun Zhang & Fengju Chen & Darshan S. Chandrashekar & Sooryanarayana Varambally & Chad J. Creighton, 2022. "Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. Ling Li & Mingming Niu & Alyssa Erickson & Jie Luo & Kincaid Rowbotham & Kai Guo & He Huang & Yuxin Li & Yi Jiang & Junguk Hur & Chunyu Liu & Junmin Peng & Xusheng Wang, 2022. "SMAP is a pipeline for sample matching in proteogenomics," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    10. Fengju Chen & Yiqun Zhang & Darshan S. Chandrashekar & Sooryanarayana Varambally & Chad J. Creighton, 2023. "Global impact of somatic structural variation on the cancer proteome," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    11. Alla D. Fedorova & Stephen J. Kiniry & Dmitry E. Andreev & Jonathan M. Mudge & Pavel V. Baranov, 2022. "Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    12. Isabelle Rose Leo & Luay Aswad & Matthias Stahl & Elena Kunold & Frederik Post & Tom Erkers & Nona Struyf & Georgios Mermelekas & Rubin Narayan Joshi & Eva Gracia-Villacampa & Päivi Östling & Olli P. , 2022. "Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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