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

被引：125

作者：

Korkut, Anil ^{[1
]}

Zaidi, Sobia ^{[2
]}

Kanchi, Rupa S. ^{[1
]}

Rao, Shuyun ^{[2
]}

Gough, Nancy R. ^{[2
]}

Schultz, Andre ^{[1
]}

Li, Xubin ^{[1
]}

Lorenzi, Philip L. ^{[1
]}

Berger, Ashton C. ^{[3
,4
]}

Robertson, Gordon ^{[5
]}

Kwong, Lawrence N. ^{[6
]}

Datto, Mike ^{[7
]}

Roszik, Jason ^{[8
]}

Ling, Shiyun ^{[1
]}

Ravikumar, Visweswaran ^{[1
]}

Manyam, Ganiraju ^{[1
]}

Rao, Arvind ^{[1
]}

Shelley, Simon ^{[9
]}

Liu, Yuexin ^{[1
]}

Ju, Zhenlin ^{[1
]}

Hansel, Donna ^{[10
]}

de Velasco, Guillermo ^{[11
,12
]}

Pennathur, Arjun ^{[13
,14
]}

Andersen, Jesper B. ^{[15
]}

O'Rourke, Colm J. ^{[15
]}

Ohshiro, Kazufumi ^{[2
]}

Jogunoori, Wilma ^{[2
,16
]}

Bao-Ngoc Nguyen ^{[2
]}

Li, Shulin ^{[17
]}

Osmanbeyoglu, Hatice U. ^{[18
]}

Ajani, Jaffer A. ^{[19
]}

Mani, Sendurai A. ^{[6
]}

Houseman, Andres ^{[20
]}

Wiznerowicz, Maciej ^{[21
,22
,23
]}

Chen, Jian ^{[24
]}

Gu, Shoujun ^{[2
]}

Ma, Wencai ^{[1
]}

Zhang, Jiexin ^{[1
]}

Tong, Pan ^{[1
]}

Cherniack, Andrew D. ^{[3
,4
]}

Deng, Chuxia ^{[2
,25
]}

Resar, Linda ^{[26
]}

Weinstein, John N. ^{[1
,27
]}

Mishra, Lopa ^{[2
,16
]}

Akbani, Rehan ^{[1
]}

机构：

[1] MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[2] George Washington Univ, Dept Surg, Ctr Translat Med, Washington, DC 20037 USA

[3] MIT, Eli & Edythe L Broad Inst, Canc Program, Cambridge, MA 02142 USA

[4] Harvard Univ, Cambridge, MA 02142 USA

[5] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada

[6] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[7] Duke Sch Med Durham, Dept Pathol, Durham, NC 27710 USA

[8] MD Anderson Canc Ctr, Dept Melanoma Med Oncol & Genom Med, Houston, TX 77030 USA

[9] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53726 USA

[10] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[11] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[12] Univ Hosp 12 Octubre, Dept Med Oncol, Madrid 28041, Spain

[13] Univ Pittsburgh, Sch Med, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA

[14] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA

[15] Univ Copenhagen, Dept Hlth & Med Sci, Biotech Res & Innovat Ctr, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark

[16] Vet Affairs Med Ctr, Inst Clin Res, Washington, DC 20422 USA

[17] Univ Texas MD Anderson Canc Ctr, Dept Pediat, Houston, TX 77030 USA

[18] Mem Sloan Kettering Canc Ctr, Computat & Syst Biol Program, 1275 York Ave, New York, NY 10021 USA

[19] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA

[20] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA

[21] Poznan Univ Med Sci, PL-61701 Poznan, Poland

[22] Greater Poland Canc Ctr, PL-61866 Poznan, Poland

[23] Int Inst Mol Oncol, PL-60203 Poznan, Poland

[24] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA

[25] Univ Macau, Fac Hlth Sci, Macau, Macau, Peoples R China

[26] Johns Hopkins Univ, Sch Med, Div Hematol Oncol & Pathol, Dept Med, Baltimore, MD 21205 USA

[27] MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

来源：

CELL SYSTEMS | 2018年 / 7卷 / 04期

关键词：

TUMOR SUPPRESSION; MUTATIONS; GENERATION; MECHANISM; PATTERNS; SEARCH; ARRAY; HMGA2;

D O I：

10.1016/j.cels.2018.08.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We present an integromic analysis of gene alterations that modulate transforming growth factor beta (TGF-beta)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-beta 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-beta ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-beta 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-beta 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-beta superfamily.

引用

页码：422 / +

页数：23

共 44 条

[1] A Pan-Cancer Analysis Reveals High Frequency Genetic Alterations in Mediators of Signaling By the TGF-β Superfamily
Zaidi, Sobia
Korkut, Anil
Chen, Jian
Rao, Shuyun
Gu, Shoujun
Ohshiro, Kazufumi
Jogunoori, Wilma S.
Mishra, Bibhuti
Akbani, Rehan
Mishra, Lopa
HEPATOLOGY, 2018, 68 : 18A - 18A
[2] A pan-cancer analysis reveals high frequency genetic alterations in mediators of signaling by the TGF-β superfamily
Ohshiro, Kazufumi
Zaidi, Sobia
Korkut, Anil
Chen, Jian
Rao, Shuyun
Gu, Shoujun
Jogunoori, Wilma
Mishra, Bibhuti
Akbani, Rehan
Mishra, Lopa
CANCER RESEARCH, 2019, 79 (13)
[3] Alterations in components of the TGF-β superfamily signaling pathways in human cancer
Levy, L
Hill, CS
CYTOKINE & GROWTH FACTOR REVIEWS, 2006, 17 (1-2) : 41 - 58
[4] A pan-cancer atlas of genomic, epigenomic and transcriptomic alterations in the TGF-β pathway
Korkut, Anil
Zaidi, Sobia
Kanchi, Rupa
Berger, Ashton C.
Robertson, Gordon
Kwong, Lawrence N.
Datto, Mike
Roszik, Jason
Ling, Shiyun
Schultz, Andre
Ravikumar, Visweswaran
Manyam, Ganiraju
Rao, Arvind
Shelley, Simon
Liu, Yuexin
Ju, Zhenlin
Hansel, Donna
de Velasco, Guillermo
Pennathur, Arjun
Andersen, Jesper B.
O'Rourke, Colm J.
Ohshiro, Kazufumi
Jogunoori, Wilma
Gough, Nancy
Li, Shulin
Osmanbeyoglu, Hatice
Houseman, Andres
Rao, Shuyun
Wiznerowicz, Maciej
Chen, Jian
Gu, Shoujun
Ma, Wencai
Zhang, Jiexin
Tong, Pan
Cherniack, Andrew D.
Deng, Chuxia
Resar-Smith, Linda
Ajani, Jaffer
Weinstein, John N.
Mishra, Lopa
Akbani, Rehan
CANCER RESEARCH, 2018, 78 (13)
[5] A pan-cancer analysis reveals the genetic alterations and immunotherapy of Piezo2 in human cancer
Liu, Xin
Jia, Yangpu
Wang, Zhihui
Zhang, Zhaoxiong
Fu, Weihua
FRONTIERS IN GENETICS, 2022, 13
[6] The role of TGF-β pathway alterations in immune regulation as a potential pan-cancer biomarker in immunotherapy
Liang, Yan
Li, Wei
Qian, Bing
Ming, Jie
Zhao, Zhengyi
Yan, Zhengqing
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ANNALS OF TRANSLATIONAL MEDICINE, 2021, 9 (22)
[7] Pan-cancer analysis of TCGA data reveals notable signaling pathways
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BMC Cancer, 15
[8] Pan-cancer analysis of TCGA data reveals notable signaling pathways
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Horvath, Curt M.
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BMC CANCER, 2015, 15
[9] A Systematic Pan-Cancer Analysis of Genetic Heterogeneity Reveals Associations with Epigenetic Modifiers
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Posa, Ioana
Carvalho, Filipa Sofia
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Grosso, Ana Rita
de Almeida, Sergio Fernandes
CANCERS, 2019, 11 (03)
[10] A pan-cancer analysis reveals genetic alterations, molecular mechanisms, and clinical relevance of m5C regulators
Du, E.
Li, Jingxian
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Li, Shuai
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Xu, Yong
Zhang, Zhihong
CLINICAL AND TRANSLATIONAL MEDICINE, 2020, 10 (05):

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