Oncogenic Signaling Pathways in The Cancer Genome Atlas

被引：2087

作者：

Sanchez-Vega, Francisco ^{[1
,2
]}

Mina, Marco ^{[5
,6
]}

Armenia, Joshua ^{[1
,2
]}

Chatila, Walid K. ^{[1
]}

Luna, Augustin ^{[7
,8
]}

La, Konnor C. ^{[1
]}

Dimitriadoy, Sofia ^{[9
]}

Liu, David L. ^{[10
,11
]}

Kantheti, Havish S. ^{[12
]}

Saghafinia, Sadegh ^{[5
,6
]}

Chakravarty, Debyani ^{[1
]}

Daian, Foysal ^{[1
]}

Gao, Qingsong ^{[13
,14
]}

Bailey, Matthew H. ^{[13
,14
]}

Liang, Wen-Wei ^{[13
,14
]}

Foltz, Steven M. ^{[13
,14
]}

Shmulevich, Ilya ^{[15
]}

Ding, Li ^{[13
,14
,16
]}

Heins, Zachary ^{[1
]}

Ochoa, Angelica ^{[1
]}

Gross, Benjamin ^{[1
]}

Gao, Jianjiong ^{[1
]}

Zhang, Hongxin ^{[1
]}

Kundra, Ritika ^{[1
]}

Kandoth, Cyriac ^{[1
]}

Bahceci, Istemi ^{[17
]}

Dervishi, Leonard ^{[17
]}

Dogrusoz, Ugur ^{[17
]}

Zhou, Wanding ^{[18
]}

Shen, Hui ^{[18
]}

Laird, Peter W. ^{[18
]}

Way, Gregory P. ^{[33
]}

Greene, Casey S. ^{[33
]}

Liang, Han ^{[34
]}

Xiao, Yonghong ^{[35
]}

Wang, Chen ^{[36
,37
]}

Iavarone, Antonio ^{[38
,39
]}

Berger, Alice H. ^{[19
]}

Bivona, Trever G. ^{[20
]}

Lazar, Alexander J. ^{[21
,22
,23
]}

Hammer, Gary D. ^{[24
]}

Giordano, Thomas ^{[25
,26
,27
]}

Kwong, Lawrence N. ^{[28
]}

McArthur, Grant ^{[29
,40
]}

Huang, Chenfei ^{[30
]}

Tward, Aaron D. ^{[31
]}

Frederick, Mitchell J. ^{[30
]}

McCormick, Frank ^{[32
]}

Meyerson, Matthew ^{[10
,11
]}

Van Allen, Eliezer M. ^{[10
,11
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Epidemiol, New York, NY 10065 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10065 USA

[5] Univ Lausanne UNIL, Dept Computat Biol, CH-1011 Lausanne, Vaud, Switzerland

[6] SIB, Lausanne, Switzerland

[7] Dana Farber Canc Inst, cBio Ctr, Boston, MA USA

[8] Harvard Med Sch, Dept Cell Biol, Boston, MA USA

[9] Princeton Univ, Princeton, NJ 08544 USA

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

[11] Broad Inst & Harvard, Canc Program, Cambridge, MA USA

[12] Univ Texas Dallas, Richardson, TX 75080 USA

[13] Washington Univ, Dept Med, St Louis, MO USA

[14] Washington Univ, McDonnell Genome Inst, St Louis, MO USA

[15] Inst Syst Biol, Seattle, WA USA

[16] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA

[17] Bilkent Univ, Comp Engn Dept, TR-06800 Ankara, Turkey

[18] Van Andel Res Inst, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA

[19] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA

[20] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, 1450 3rd St, San Francisco, CA 94143 USA

[21] Univ Texas MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd Unit 85, Houston, TX 77030 USA

[22] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, 1515 Holcombe Blvd Unit 85, Houston, TX 77030 USA

[23] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, 1515 Holcombe Blvd Unit 85, Houston, TX 77030 USA

[24] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Endocrine Oncol Program, Ann Arbor, MI USA

[25] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA

[26] Univ Michigan, Sch Med, Dept Internal Med, Div Metab, Ann Arbor, MI USA

[27] Michigan Med, Comprehens Canc Ctr, Ann Arbor, MI USA

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

[29] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[30] Baylor Coll Med, Dept Otolaryngol, Houston, TX 77030 USA

[31] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, 2233 Post St, San Francisco, CA 94143 USA

[32] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, 1450 3rd St, San Francisco, CA 94143 USA

[33] Univ Pennsylvania, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA USA

[34] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX USA

[35] TESARO Inc, Waltham, MA 02451 USA

[36] Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 First St SW, Rochester, MN USA

[37] Mayo Clin, Coll Med, Dept Obstet & Gynecol, 200 First St SW, Rochester, MN USA

[38] Columbia Univ, Med Ctr, Inst Canc Genet, Dept Neurol, New York, NY 10032 USA

[39] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA

[40] Univ Melbourne, Melbourne, Vic, Australia

来源：

CELL | 2018年 / 173卷 / 02期

关键词：

COMPREHENSIVE MOLECULAR CHARACTERIZATION; LANDSCAPE; GENES; EXPRESSION; SIGNATURES; MUTATIONS;

D O I：

10.1016/j.cell.2018.03.035

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：

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.

引用

页码：321 / +

页数：27

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