Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

被引：1201

作者：

Robertson, A. Gordon ^{[1
]}

Kim, Jaegil ^{[2
]}

Al-Ahmadie, Hikmat ^{[3
]}

Bellmunt, Joaquim ^{[4
,5
]}

Guo, Guangwu ^{[5
,6
]}

Cherniack, Andrew D. ^{[2
]}

Hinoue, Toshinori ^{[7
]}

Laird, Peter W. ^{[7
]}

Hoadley, Katherine A. ^{[8
]}

Akbani, Rehan ^{[9
]}

Castro, Mauro A. A. ^{[10
]}

Gibb, Ewan A. ^{[1
]}

Kanchi, Rupa S. ^{[9
]}

Gordenin, Dmitry A. ^{[11
]}

Shukla, Sachet A. ^{[5
,6
]}

Sanchez-Vega, Francisco ^{[12
]}

Hansel, Donna E. ^{[13
]}

Czerniak, Bogdan A. ^{[14
]}

Reuter, Victor E. ^{[3
]}

Su, Xiaoping ^{[9
]}

Carvalho, Benilton de Sa ^{[15
]}

Chagas, Vinicius S. ^{[10
]}

Mungall, Karen L. ^{[1
]}

Sadeghi, Sara ^{[1
]}

Pedamallu, Chandra Sekhar ^{[2
]}

Lu, Yiling ^{[16
]}

Klimczak, Leszek J. ^{[17
]}

Zhang, Jiexin ^{[9
]}

Choo, Caleb ^{[1
]}

Ojesina, Akinyemi I. ^{[18
]}

Bullman, Susan ^{[2
]}

Leraas, Kristen M. ^{[19
]}

Lichtenberg, Tara M. ^{[19
]}

Wu, Catherine J. ^{[20
]}

Schultz, Nicholaus ^{[12
]}

Getz, Gad ^{[2
]}

Meyerson, Matthew ^{[5
,21
]}

Mills, Gordon B. ^{[16
]}

McConkey, David J. ^{[22
]}

Weinstein, John N. ^{[9
,16
]}

Kwiatkowski, David J. ^{[23
]}

Lerner, Seth P. ^{[24
]}

机构：

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

[2] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA

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

[4] Dana Farber Canc Inst, Bladder Canc Ctr, Dept Med, PSMAR IMIM Lab, Boston, MA 02215 USA

[5] Harvard Univ, Boston, MA 02115 USA

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

[7] Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA

[8] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27514 USA

[9] Univ Texas Houston, MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA

[10] Univ Fed Parana, Polytech Ctr, Bioinformat & Syst Biol Lab, BR-80060000 Curitiba, Parana, Brazil

[11] NIEHS, NIH, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA

[12] Mem Sloan Kettering Canc Ctr, Ctr Mol Oncol, New York, NY 10065 USA

[13] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA

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

[15] Univ Estadual Campinas, Dept Stat, Biostat & Computat Biol Lab, BR-13083859 Sao Paulo, Brazil

[16] Univ Texas Houston, MD Anderson Canc Ctr, Dept Syst Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA

[17] NIEHS, NIH, Integrat Bioinformat Support Grp, POB 12233, Res Triangle Pk, NC 27709 USA

[18] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA

[19] Res Inst Nationwide Childrens Hosp, Biospecimen Core Resource, Columbus, OH 43205 USA

[20] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA

[21] Dana Farber Canc Inst, Pathol & Med Oncol, Boston, MA 02115 USA

[22] Johns Hopkins Univ, Greenberg Bladder Canc Inst, Baltimore, MD 21218 USA

[23] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[24] Baylor Coll Med, Dan L Duncan Canc Ctr, Scott Dept Urol, Houston, TX 77030 USA

来源：

CELL | 2017年 / 171卷 / 03期

关键词：

SOMATIC ERCC2 MUTATIONS; PHASE PROTEIN ARRAY; UROTHELIAL CARCINOMA; GENETIC ALTERATIONS; LUMINAL SUBTYPES; EXPRESSION; RECEPTOR; ACCURATE; BASAL; QUANTIFICATION;

D O I：

10.1016/j.cell.2017.09.007

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 report a comprehensive analysis of 412 muscleinvasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal'' subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA ( lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

引用

页码：540 / +

页数：42

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