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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily. / Cancer Genome Atlas Research Network.

In: Cell Systems, Vol. 7, No. 4, 2018, p. 422-437.e1-e7.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Cancer Genome Atlas Research Network 2018, 'A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily', Cell Systems, vol. 7, no. 4, pp. 422-437.e1-e7. https://doi.org/10.1016/j.cels.2018.08.010

APA

Cancer Genome Atlas Research Network (2018). A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily. Cell Systems, 7(4), 422-437.e1-e7. https://doi.org/10.1016/j.cels.2018.08.010

Vancouver

Cancer Genome Atlas Research Network. A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily. Cell Systems. 2018;7(4):422-437.e1-e7. https://doi.org/10.1016/j.cels.2018.08.010

Author

Cancer Genome Atlas Research Network. / A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily. In: Cell Systems. 2018 ; Vol. 7, No. 4. pp. 422-437.e1-e7.

Bibtex

@article{13481918e2bb4ba1b12ef952c7e95ae9,

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

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.",

author = "Anil Korkut and Sobia Zaidi and Kanchi, {Rupa S} and Shuyun Rao and Gough, {Nancy R} and Andre Schultz and Xubin Li and Lorenzi, {Philip L} and Berger, {Ashton C} and Gordon Robertson and Kwong, {Lawrence N} and Mike Datto and Jason Roszik and Shiyun Ling and Visweswaran Ravikumar and Ganiraju Manyam and Arvind Rao and Simon Shelley and Yuexin Liu and Zhenlin Ju and Donna Hansel and {de Velasco}, Guillermo and Arjun Pennathur and Andersen, {Jesper B} and O'Rourke, {Colm J} and Kazufumi Ohshiro and Wilma Jogunoori and Bao-Ngoc Nguyen and Shulin Li and Osmanbeyoglu, {Hatice U} and Ajani, {Jaffer A} and Mani, {Sendurai A} and Andres Houseman and Maciej Wiznerowicz and Jian Chen and Shoujun Gu and Wencai Ma and Jiexin Zhang and Pan Tong and Cherniack, {Andrew D} and Chuxia Deng and Linda Resar and Weinstein, {John N} and Lopa Mishra and Rehan Akbani and {Cancer Genome Atlas Research Network}",

year = "2018",

doi = "10.1016/j.cels.2018.08.010",

language = "English",

volume = "7",

pages = "422--437.e1--e7",

journal = "Cell Systems",

issn = "2405-4712",

publisher = "Cell Press",

number = "4",

}

RIS

TY - JOUR

T1 - A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily

AU - Korkut, Anil

AU - Zaidi, Sobia

AU - Kanchi, Rupa S

AU - Rao, Shuyun

AU - Gough, Nancy R

AU - Schultz, Andre

AU - Li, Xubin

AU - Lorenzi, Philip L

AU - Berger, Ashton C

AU - Robertson, Gordon

AU - Kwong, Lawrence N

AU - Datto, Mike

AU - Roszik, Jason

AU - Ling, Shiyun

AU - Ravikumar, Visweswaran

AU - Manyam, Ganiraju

AU - Rao, Arvind

AU - Shelley, Simon

AU - Liu, Yuexin

AU - Ju, Zhenlin

AU - Hansel, Donna

AU - de Velasco, Guillermo

AU - Pennathur, Arjun

AU - Andersen, Jesper B

AU - O'Rourke, Colm J

AU - Ohshiro, Kazufumi

AU - Jogunoori, Wilma

AU - Nguyen, Bao-Ngoc

AU - Li, Shulin

AU - Osmanbeyoglu, Hatice U

AU - Ajani, Jaffer A

AU - Mani, Sendurai A

AU - Houseman, Andres

AU - Wiznerowicz, Maciej

AU - Chen, Jian

AU - Gu, Shoujun

AU - Ma, Wencai

AU - Zhang, Jiexin

AU - Tong, Pan

AU - Cherniack, Andrew D

AU - Deng, Chuxia

AU - Resar, Linda

AU - Weinstein, John N

AU - Mishra, Lopa

AU - Akbani, Rehan

AU - Cancer Genome Atlas Research Network

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1016/j.cels.2018.08.010

DO - 10.1016/j.cels.2018.08.010

M3 - Journal article

C2 - 30268436

VL - 7

SP - 422-437.e1-e7

JO - Cell Systems

JF - Cell Systems

SN - 2405-4712

IS - 4

ER -

ID: 209256866