Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

被引：329

作者：

Seiler, Michael ^{[1
]}

Peng, Shouyong ^{[1
]}

Agrawal, Anant A. ^{[1
]}

Palacino, James ^{[1
]}

Teng, Teng ^{[1
]}

Zhu, Ping ^{[1
]}

Smith, Peter G. ^{[1
]}

Buonamici, Silvia ^{[1
]}

Yu, Lihua ^{[1
]}

机构：

[1] H3 Biomed Inc, 300 Technol Sq, Cambridge, MA 02139 USA

来源：

CELL REPORTS | 2018年 / 23卷 / 01期

关键词：

FAR UPSTREAM ELEMENT; U2AF1; MUTATIONS; RNA-BINDING; C-MYC; SPLICEOSOME; SF3B1; GENOME; EXPRESSION; PATHWAY; SRSF2;

D O I：

10.1016/j.celrep.2018.01.088

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis.

引用

页码：282 / +

页数：19

共 68 条

[1] Genomic Classification of Cutaneous Melanoma [J].

Akbani, Rehan ;

Akdemir, Kadir C. ;

Aksoy, B. Arman ;

Albert, Monique ;

Ally, Adrian ;

Amin, Samirkumar B. ;

Arachchi, Harindra ;

Arora, Arshi ;

Auman, J. Todd ;

Ayala, Brenda ;

Baboud, Julien ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barnabas, Nandita ;

Bartlett, John ;

Bartlett, Pam ;

Bastian, Boris C. ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Belyaev, Dmitry ;

Benz, Christopher ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bir, Natalie ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Boland, Genevieve M. ;

Bono, Riccardo ;

Bootwalla, Moiz S. ;

Bosenberg, Marcus ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brockway-Lunardi, Laura ;

Brooks, Denise ;

Brzezinski, Jakub ;

Bshara, Wiam ;

Buda, Elizabeth ;

Burns, William R. ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Calderone, Tiffany ;

Cappellini, Giancarlo Antonini ;

Carter, Candace ;

Carter, Scott L. ;

Cherney, Lynn ;

Cherniack, Andrew D. ;

Chevalier, Aaron ;

Chin, Lynda .

CELL, 2015, 161 (07) :1681-1696

[2] SRSF1-Regulated Alternative Splicing in Breast Cancer [J].

Anczukow, Olga ;

Akerman, Martin ;

Clery, Antoine ;

Wu, Jie ;

Shen, Chen ;

Shirole, Nitin H. ;

Raimer, Amanda ;

Sun, Shuying ;

Jensen, Mads A. ;

Hua, Yimin ;

Allain, Frederic H. -T. ;

Krainer, Adrian R. .

MOLECULAR CELL, 2015, 60 (01) :105-117

[3]

[Anonymous], 2011, R: A Language and Environment for Statistical Computing

[4] Systematic genome-wide annotation of spliceosomal proteins reveals differential gene family expansion [J].

Barbosa-Morais, NL ;

Carmo-Fonseca, M ;

Aparício, S .

GENOME RESEARCH, 2006, 16 (01) :66-77

[5] RBM5, 6, and 10 Differentially Regulate NUMB Alternative Splicing to Control Cancer Cell Proliferation [J].

Bechara, Elias G. ;

Sebestyen, Endre ;

Bernardis, Isabella ;

Eyras, Eduardo ;

Valcarcel, Juan .

MOLECULAR CELL, 2013, 52 (05) :720-733

[6] Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes [J].

Biankin, Andrew V. ;

Waddell, Nicola ;

Kassahn, Karin S. ;

Gingras, Marie-Claude ;

Muthuswamy, Lakshmi B. ;

Johns, Amber L. ;

Miller, David K. ;

Wilson, Peter J. ;

Patch, Ann-Marie ;

Wu, Jianmin ;

Chang, David K. ;

Cowley, Mark J. ;

Gardiner, Brooke B. ;

Song, Sarah ;

Harliwong, Ivon ;

Idrisoglu, Senel ;

Nourse, Craig ;

Nourbakhsh, Ehsan ;

Manning, Suzanne ;

Wani, Shivangi ;

Gongora, Milena ;

Pajic, Marina ;

Scarlett, Christopher J. ;

Gill, Anthony J. ;

Pinho, Andreia V. ;

Rooman, Ilse ;

Anderson, Matthew ;

Holmes, Oliver ;

Leonard, Conrad ;

Taylor, Darrin ;

Wood, Scott ;

Xu, Qinying ;

Nones, Katia ;

Fink, J. Lynn ;

Christ, Angelika ;

Bruxner, Tim ;

Cloonan, Nicole ;

Kolle, Gabriel ;

Newell, Felicity ;

Pinese, Mark ;

Mead, R. Scott ;

Humphris, Jeremy L. ;

Kaplan, Warren ;

Jones, Marc D. ;

Colvin, Emily K. ;

Nagrial, Adnan M. ;

Humphrey, Emily S. ;

Chou, Angela ;

Chin, Venessa T. ;

Chantrill, Lorraine A. .

NATURE, 2012, 491 (7424) :399-405

[7] 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

[8] Near-optimal probabilistic RNA-seq quantification (vol 34, pg 525, 2016) [J].

Bray, Nicolas L. ;

Pimentel, Harold ;

Melsted, Pall ;

Pachter, Lior .

NATURE BIOTECHNOLOGY, 2016, 34 (08) :888-888

[9] A Pan-Cancer Analysis of Transcriptome Changes Associated with Somatic Mutations in U2AF1 Reveals Commonly Altered Splicing Events [J].

Brooks, Angela N. ;

Choi, Peter S. ;

de Waal, Luc ;

Sharifnia, Tanaz ;

Imielinski, Marcin ;

Saksena, Gordon ;

Pedamallu, Chandra Sekhar ;

Sivachenko, Andrey ;

Rosenberg, Mara ;

Chmielecki, Juliann ;

Lawrence, Michael S. ;

DeLuca, David S. ;

Getz, Gad ;

Meyerson, Matthew .

PLOS ONE, 2014, 9 (01)

[10] Comprehensive molecular profiling of lung adenocarcinoma [J].

Collisson, Eric A. ;

Campbell, Joshua D. ;

Brooks, Angela N. ;

Berger, Alice H. ;

Lee, William ;

Chmielecki, Juliann ;

Beer, David G. ;

Cope, Leslie ;

Creighton, Chad J. ;

Danilova, Ludmila ;

Ding, Li ;

Getz, Gad ;

Hammerman, Peter S. ;

Hayes, D. Neil ;

Hernandez, Bryan ;

Herman, James G. ;

Heymach, John V. ;

Jurisica, Igor ;

Kucherlapati, Raju ;

Kwiatkowski, David ;

Ladanyi, Marc ;

Robertson, Gordon ;

Schultz, Nikolaus ;

Shen, Ronglai ;

Sinha, Rileen ;

Sougnez, Carrie ;

Tsao, Ming-Sound ;

Travis, William D. ;

Weinstein, John N. ;

Wigle, Dennis A. ;

Wilkerson, Matthew D. ;

Chu, Andy ;

Cherniack, Andrew D. ;

Hadjipanayis, Angela ;

Rosenberg, Mara ;

Weisenberger, Daniel J. ;

Laird, Peter W. ;

Radenbaugh, Amie ;

Ma, Singer ;

Stuart, Joshua M. ;

Byers, Lauren Averett ;

Baylin, Stephen B. ;

Govindan, Ramaswamy ;

Meyerson, Matthew ;

Rosenberg, Mara ;

Gabriel, Stacey B. ;

Cibulskis, Kristian ;

Sougnez, Carrie ;

Kim, Jaegil ;

Stewart, Chip .

NATURE, 2014, 511 (7511) :543-550

← 1 2 3 4 5 6 7 →