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

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