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A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily

Overview of attention for article published in Cell Systems, September 2018
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Title
A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily
Published in
Cell Systems, September 2018
DOI 10.1016/j.cels.2018.08.010
Pubmed ID
Authors

Anil Korkut, Sobia Zaidi, Rupa S. Kanchi, Shuyun Rao, Nancy R. Gough, Andre Schultz, Xubin Li, Philip L. Lorenzi, Ashton C. Berger, Gordon Robertson, Lawrence N. Kwong, Mike Datto, Jason Roszik, Shiyun Ling, Visweswaran Ravikumar, Ganiraju Manyam, Arvind Rao, Simon Shelley, Yuexin Liu, Zhenlin Ju, Donna Hansel, Guillermo de Velasco, Arjun Pennathur, Jesper B. Andersen, Colm J. O'Rourke, Kazufumi Ohshiro, Wilma Jogunoori, Bao-Ngoc Nguyen, Shulin Li, Hatice U. Osmanbeyoglu, Jaffer A. Ajani, Sendurai A. Mani, Andres Houseman, Maciej Wiznerowicz, Jian Chen, Shoujun Gu, Wencai Ma, Jiexin Zhang, Pan Tong, Andrew D. Cherniack, Chuxia Deng, Linda Resar, John N. Weinstein, Lopa Mishra, Rehan Akbani, Amy Blum, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Peggy Wang, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. 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Wendl, Cecilia Williams, Joseph Willis, Denise Wolf, Karen Wong, Yonghong Xiao, Lu Xinghua, Bo Yang, Da Yang, Liuqing Yang, Kai Ye, Hiroyuki Yoshida, Lihua Yu, Sobia Zaidi, Huiwen Zhang, Min Zhang, Xiaoyang Zhang, Tianhao Zhao, Wei Zhao, Zhongming Zhao, Tian Zheng, Jane Zhou, Zhicheng Zhou, Hongtu Zhu, Ping Zhu, Michael T. Zimmermann, Elad Ziv, Patrick A. Zweidler-McKay

Abstract

We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-β superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-β signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily.

Twitter Demographics

The data shown below were collected from the profiles of 51 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 32%
Researcher 9 24%
Student > Master 5 13%
Student > Bachelor 3 8%
Student > Postgraduate 3 8%
Other 6 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 26%
Medicine and Dentistry 9 24%
Agricultural and Biological Sciences 9 24%
Immunology and Microbiology 6 16%
Unspecified 2 5%
Other 2 5%

Attention Score in Context

This research output has an Altmetric Attention Score of 26. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 December 2018.
All research outputs
#546,924
of 12,503,295 outputs
Outputs from Cell Systems
#142
of 468 outputs
Outputs of similar age
#21,997
of 260,138 outputs
Outputs of similar age from Cell Systems
#13
of 29 outputs
Altmetric has tracked 12,503,295 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 468 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 28.8. This one has gotten more attention than average, scoring higher than 69% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 260,138 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.