Systematic pan-cancer analysis of tumour purity

被引:830
作者
Aran, Dvir [1 ,2 ]
Sirota, Marina [1 ]
Butte, Atul J. [1 ]
机构
[1] Univ Calif San Francisco, Inst Computat Hlth Sci, San Francisco, CA 94158 USA
[2] Stanford Univ, Dept Pediat, Div Syst Med, Stanford, CA 94305 USA
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
基金
美国国家卫生研究院;
关键词
GENOMIC ANALYSIS; DECONVOLUTION; SUBTYPES; CLASSIFICATION; HETEROGENEITY; BLOCKADE; PATTERNS; TISSUE;
D O I
10.1038/ncomms9971
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
The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results. Here we present a systematic analysis using different measurement modalities of tumour purity in > 10,000 samples across 21 cancer types from the Cancer Genome Atlas. Patients are stratified according to clinical features in an attempt to detect clinical differences driven by purity levels. We demonstrate the confounding effect of tumour purity on correlating and clustering tumours with transcriptomics data. Finally, using a differential expression method that accounts for tumour purity, we find an immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses.
引用
收藏
页数:11
相关论文
共 41 条
[1]   Deconvolution of Blood Microarray Data Identifies Cellular Activation Patterns in Systemic Lupus Erythematosus [J].
Abbas, Alexander R. ;
Wolslegel, Kristen ;
Seshasayee, Dhaya ;
Modrusan, Zora ;
Clark, Hilary F. .
PLOS ONE, 2009, 4 (07)
[2]   A pan-cancer proteomic perspective on The Cancer Genome Atlas [J].
Akbani, Rehan ;
Ng, Patrick Kwok Shing ;
Werner, Henrica M. J. ;
Shahmoradgoli, Maria ;
Zhang, Fan ;
Ju, Zhenlin ;
Liu, Wenbin ;
Yang, Ji-Yeon ;
Yoshihara, Kosuke ;
Li, Jun ;
Ling, Shiyun ;
Seviour, Elena G. ;
Ram, Prahlad T. ;
Minna, John D. ;
Diao, Lixia ;
Tong, Pan ;
Heymach, John V. ;
Hill, Steven M. ;
Dondelinger, Frank ;
Stadler, Nicolas ;
Byers, Lauren A. ;
Meric-Bernstam, Funda ;
Weinstein, John N. ;
Broom, Bradley M. ;
Verhaak, Roeland G. W. ;
Liang, Han ;
Mukherjee, Sach ;
Lu, Yiling ;
Mills, Gordon B. .
NATURE COMMUNICATIONS, 2014, 5
[3]   EXPANDS: expanding ploidy and allele frequency on nested subpopulations [J].
Andor, Noemi ;
Harness, Julie V. ;
Muller, Sabine ;
Mewes, Hans W. ;
Petritsch, Claudia .
BIOINFORMATICS, 2014, 30 (01) :50-60
[4]   Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas [J].
Brat, Daniel J. ;
Verhaak, Roel G. W. ;
Al-dape, Kenneth D. ;
Yung, W. K. Alfred ;
Salama, Sofie R. ;
Cooper, Lee A. D. ;
Rheinbay, Esther ;
Miller, C. Ryan ;
Vitucci, Mark ;
Morozova, Olena ;
Robertson, A. Gordon ;
Noushmehr, Houtan ;
Laird, Peter W. ;
Cherniack, Andrew D. ;
Akbani, Rehan ;
Huse, Jason T. ;
Ciriello, Giovanni ;
Poisson, Laila M. ;
Barnholtz-Sloan, Jill S. ;
Berger, Mitchel S. ;
Brennan, Cameron ;
Colen, Rivka R. ;
Colman, Howard ;
Flanders, Adam E. ;
Giannini, Caterina ;
Grifford, Mia ;
Iavarone, Antonio ;
Jain, Rajan ;
Joseph, Isaac ;
Kim, Jaegil ;
Kasaian, Katayoon ;
Mikkelsen, Tom ;
Murray, Bradley A. ;
O'Neill, Brian Patrick ;
Pachter, Lior ;
Parsons, Donald W. ;
Sougnez, Carrie ;
Sulman, Erik P. ;
Vandenberg, Scott R. ;
Van Meir, Erwin G. ;
von Deimling, Andreas ;
Zhang, Hailei ;
Crain, Daniel ;
Lau, Kevin ;
Mallery, David ;
Morris, Scott ;
Paulauskis, Joseph ;
Penny, Robert ;
Shelton, Troy ;
Sherman, Mark .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) :2481-2498
[5]   Absolute quantification of somatic DNA alterations in human cancer [J].
Carter, Scott L. ;
Cibulskis, Kristian ;
Helman, Elena ;
McKenna, Aaron ;
Shen, Hui ;
Zack, Travis ;
Laird, Peter W. ;
Onofrio, Robert C. ;
Winckler, Wendy ;
Weir, Barbara A. ;
Beroukhim, Rameen ;
Pellman, David ;
Levine, Douglas A. ;
Lander, Eric S. ;
Meyerson, Matthew ;
Getz, Gad .
NATURE BIOTECHNOLOGY, 2012, 30 (05) :413-+
[6]   Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial [J].
Carthon, Bradley C. ;
Wolchok, Jedd D. ;
Yuan, Jianda ;
Kamat, Ashish ;
Tang, Derek S. Ng ;
Sun, Jingjing ;
Ku, Geoffrey ;
Troncoso, Patricia ;
Logothetis, Christopher J. ;
Allison, James P. ;
Sharma, Padmanee .
CLINICAL CANCER RESEARCH, 2010, 16 (10) :2861-2871
[7]   Allele-specific copy number profiling by next-generation DNA sequencing [J].
Chen, Hao ;
Bell, John M. ;
Zavala, Nicolas A. ;
Ji, Hanlee P. ;
Zhang, Nancy R. .
NUCLEIC ACIDS RESEARCH, 2015, 43 (04)
[8]   Molecular portraits and the family tree of cancer [J].
Chung, CH ;
Bernard, PS ;
Perou, CM .
NATURE GENETICS, 2002, 32 (Suppl 4) :533-540
[9]   Systematic Bias in Genomic Classification Due to Contaminating Non-neoplastic Tissue in Breast Tumor Samples [J].
Elloumi, Fathi ;
Hu, Zhiyuan ;
Li, Yan ;
Parker, Joel S. ;
Gulley, Margaret L. ;
Amos, Keith D. ;
Troester, Melissa A. .
BMC MEDICAL GENOMICS, 2011, 4
[10]   Immunity, Inflammation, and Cancer [J].
Grivennikov, Sergei I. ;
Greten, Florian R. ;
Karin, Michael .
CELL, 2010, 140 (06) :883-899