Comprehensive Characterization of Cancer Driver Genes and Mutations

Комплексная характеристика генов и мутаций — драйверов рака
Jiexin Zhang, John N. Weinstein, Peter J. Park, Brady Bernard, Ilya Shmulevich, Gad Getz, Kalle Leinonen, Sheila M. Reynolds, Vésteinn Thórsson, Martin L. Ferguson, John A. Demchok, Roy Tarnuzzer, Linghua Wang, Liming Yang, Heidi J. Sofia, Todd Pihl, Yunhu Wan, Juok Cho, Scott Frazer, Nils Gehlenborg, David I. Heiman, Michael S. Lawrence, Gordon Saksena, Doug Voet, Rehan Akbani, Yuexin Liu, Yiling Lu, Matthew H. Bailey, Song Cao, Michael C. Wendl, Michael Miller, Zixing Wang, Hailei Zhang, Jaegil Kim, Eliezer M. Van Allen, Qiang Sun, Rory Johnson, Shiyun Ling, Jun Li, Wei Zhang, Isidro Cortés‐Ciriano, Julian M. Hess, Joshua Armenia, Timothy Defreitas, Ina Felau, Abel González-Pérez, Apurva M. Hegde, Carolyn M. Hutter, Ekta Khurana, Eric Minwei Liu, Loris Mularoni, Michael S. Noble, Carlota Rubio-Pérez, David Tamborero, Jean C. Zenklusen, Jiashan Zhang, Han Liang, Brendan Reardon, Zhining Wang, Gordon B. Mills, Denis Bertrand, Melpomeni Kasapi, Niranjan Nagarajan, Wen-Wei Liang, Zhenlin Ju, Galen F. Gao, Antonio Colaprico, Qingsong Gao, Sudha Chudamani, Ye Wu, Theo Knijnenburg, Pei Lin, Rashi Naresh, Daniel Cui Zhou, Adam Abeshouse, Eduard Porta‐Pardo, Varsha Dhankani, Melpomeni Kasapi, Laxmi Lolla, Sam Meier, Nyasha Chambwe, Roger Kramer, Bradley M. Broom, Rupa S. Kanchi, Anil Korkut, Kwok-Shing Ng, Michael P. Ryan, Wenbin Liu, Jia Liu, Arvind Rao, Patrick Kwok‐Shing Ng, Sohini Sengupta, Venkata Yellapantula, Amila Weerasinghe, Collin Tokheim, Chayaporn Suphavilai, Kang Jin Jeong, Fang Wang, Jia Yu Ko, Han Liang, Jing Wang
2018-04-01

PanCancer analysiscancer driver genesclinically actionable eventsdriver mutationsprecision oncology
Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%-85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors.
1
A PanCancer and PanSoftware analysis of 9,423 tumor exomes across all 33 TCGA projects used 26 computational tools to identify cancer drivers.
2
Experimental validation indicated that 60%–85% of predicted mutations were likely cancer drivers.
3
More than 300 microsatellite-instability tumors showed high PD-1/PD-L1 levels, and 57% of analyzed tumors harbored putative clinically actionable events.
4
Sequence- and structure-based analyses uncovered more than 3,400 putative missense driver mutations supported by multiple lines of evidence.
5
The study identified 299 driver genes and characterized their associations with anatomical sites and cancer or cell types.

Cancer driver genes and mutations across tumors from all 33 The Cancer Genome Atlas projects

The identification, characterization, and clinical relevance of driver genes and putative driver mutations, including their cancer-type, anatomical-site, molecular, and actionable associations

Publication Details
Publication Date
2018-04-01
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Authors
Jiexin Zhang
John N. Weinstein
Peter J. Park
Brady Bernard
Ilya Shmulevich
Gad Getz
Kalle Leinonen
Sheila M. Reynolds
Vésteinn Thórsson
Martin L. Ferguson
John A. Demchok
Roy Tarnuzzer
Linghua Wang
Liming Yang
Heidi J. Sofia
Todd Pihl
Yunhu Wan
Juok Cho
Scott Frazer
Nils Gehlenborg
David I. Heiman
Michael S. Lawrence
Gordon Saksena
Doug Voet
Rehan Akbani
Yuexin Liu
Yiling Lu
Matthew H. Bailey
Song Cao
Michael C. Wendl
Michael Miller
Zixing Wang
Hailei Zhang
Jaegil Kim
Eliezer M. Van Allen
Qiang Sun
Rory Johnson
Shiyun Ling
Jun Li
Wei Zhang
Isidro Cortés‐Ciriano
Julian M. Hess
Joshua Armenia
Timothy Defreitas
Ina Felau
Abel González-Pérez
Apurva M. Hegde
Carolyn M. Hutter
Ekta Khurana
Eric Minwei Liu
Loris Mularoni
Michael S. Noble
Carlota Rubio-Pérez
David Tamborero
Jean C. Zenklusen
Jiashan Zhang
Han Liang
Brendan Reardon
Zhining Wang
Gordon B. Mills
Denis Bertrand
Melpomeni Kasapi
Niranjan Nagarajan
Wen-Wei Liang
Zhenlin Ju
Galen F. Gao
Antonio Colaprico
Qingsong Gao
Sudha Chudamani
Ye Wu
Theo Knijnenburg
Pei Lin
Rashi Naresh
Daniel Cui Zhou
Adam Abeshouse
Eduard Porta‐Pardo
Varsha Dhankani
Melpomeni Kasapi
Laxmi Lolla
Sam Meier
Nyasha Chambwe
Roger Kramer
Bradley M. Broom
Rupa S. Kanchi
Anil Korkut
Kwok-Shing Ng
Michael P. Ryan
Wenbin Liu
Jia Liu
Arvind Rao
Patrick Kwok‐Shing Ng
Sohini Sengupta
Venkata Yellapantula
Amila Weerasinghe
Collin Tokheim
Chayaporn Suphavilai
Kang Jin Jeong
Fang Wang
Jia Yu Ko
Han Liang
Jing Wang
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