The mutational landscape of adenoid cystic carcinoma

被引：371

作者：

Ho, Allen S. ^{[1
,2
]}

Kannan, Kasthuri ^{[1
]}

Roy, David M. ^{[1
]}

Morris, Luc G. T. ^{[1
,2
]}

Ganly, Ian ^{[1
,2
]}

Katabi, Nora ^{[3
]}

Ramaswami, Deepa ^{[1
]}

Walsh, Logan A. ^{[1
]}

Eng, Stephanie ^{[1
]}

Huse, Jason T. ^{[1
,3
]}

Zhang, Jianan ^{[1
]}

Dolgalev, Igor ^{[1
]}

Huberman, Kety ^{[1
]}

Heguy, Adriana ^{[1
]}

Viale, Agnes ^{[4
]}

Drobnjak, Marija ^{[5
]}

Leversha, Margaret A. ^{[6
]}

Rice, Christine E. ^{[6
]}

Singh, Bhuvanesh ^{[2
]}

Iyer, N. Gopalakrishna ^{[7
]}

Leemans, C. Rene ^{[8
]}

Bloemena, Elisabeth ^{[9
]}

Ferris, Robert L. ^{[10
]}

Seethala, Raja R. ^{[11
]}

Gross, Benjamin E. ^{[12
]}

Liang, Yupu ^{[12
]}

Sinha, Rileen ^{[12
]}

Peng, Luke ^{[1
]}

Raphael, Benjamin J. ^{[13
]}

Turcan, Sevin ^{[1
]}

Gong, Yongxing ^{[1
]}

Schultz, Nikolaus ^{[14
]}

Kim, Seungwon ^{[10
]}

Chiosea, Simion ^{[11
]}

Shah, Jatin P. ^{[2
]}

Sander, Chris ^{[12
]}

Lee, William ^{[12
]}

Chan, Timothy A. ^{[1
,14
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA

[4] Mem Sloan Kettering Canc Ctr, Genom Core, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Pathol Core, New York, NY 10021 USA

[6] Mem Sloan Kettering Canc Ctr, Mol Cytogenet Core, New York, NY 10021 USA

[7] Natl Canc Ctr Singapore, Dept Surg Oncol, Singapore, Singapore

[8] Vrije Univ Amsterdam, Med Ctr, Dept Otolaryngol Head & Neck Surg, Amsterdam, Netherlands

[9] Vrije Univ Amsterdam, Med Ctr, Acad Ctr Dent, Dept Oral & Maxillofacial Surg & Oral Pathol, Amsterdam, Netherlands

[10] Univ Pittsburgh, Med Ctr, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA USA

[11] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA

[12] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA

[13] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA

[14] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 07期

基金：

美国国家卫生研究院;

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; CHROMATIN REMODELING GENES; SOMATIC POINT MUTATIONS; SQUAMOUS-CELL CARCINOMA; DNA-SEQUENCING DATA; BREAST-CANCER; TUMOR-GROWTH; INACTIVATING MUTATIONS; MISSENSE MUTATIONS; PROSTATE-CANCER;

D O I：

10.1038/ng.2643

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Adenoid cystic carcinomas (ACCs) are among the most enigmatic of human malignancies. These aggressive salivary gland cancers frequently recur and metastasize despite definitive treatment, with no known effective chemotherapy regimen. Here we determined the ACC mutational landscape and report the exome or whole-genome sequences of 60 ACC tumor-normal pairs. These analyses identified a low exonic somatic mutation rate (0.31 non-silent events per megabase) and wide mutational diversity. Notably, we found mutations in genes encoding chromatin-state regulators, such as SMARCA2, CREBBP and KDM6A, suggesting that there is aberrant epigenetic regulation in ACC oncogenesis. Mutations in genes central to the DNA damage response and protein kinase A signaling also implicate these processes. We observed MYB-NFIB translocations and somatic mutations in MYB-associated genes, solidifying the role of these aberrations as critical events in ACC. Lastly, we identified recurrent mutations in the FGF-IGF-PI3K pathway (30% of tumors) that might represent new avenues for therapy. Collectively, our observations establish a molecular foundation for understanding and exploring new treatments for ACC.

引用

页码：791 / +

页数：10

共 98 条

[1] Ryanodine receptor expression correlates with tumor grade in breast cancer [J].

Abdul, Mansoor ;

Ramlal, Sian ;

Hoosein, Naseema .

PATHOLOGY & ONCOLOGY RESEARCH, 2008, 14 (02) :157-160

[2] Biology and Management of Salivary Gland Cancers [J].

Adelstein, David J. ;

Koyfman, Shlomo A. ;

El-Naggar, Adel K. ;

Hanna, Ehab Y. .

SEMINARS IN RADIATION ONCOLOGY, 2012, 22 (03) :245-253

[3] Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1 [J].

Agrawal, Nishant ;

Frederick, Mitchell J. ;

Pickering, Curtis R. ;

Bettegowda, Chetan ;

Chang, Kyle ;

Li, Ryan J. ;

Fakhry, Carole ;

Xie, Tong-Xin ;

Zhang, Jiexin ;

Wang, Jing ;

Zhang, Nianxiang ;

El-Naggar, Adel K. ;

Jasser, Samar A. ;

Weinstein, John N. ;

Trevino, Lisa ;

Drummond, Jennifer A. ;

Muzny, Donna M. ;

Wu, Yuanqing ;

Wood, Laura D. ;

Hruban, Ralph H. ;

Westra, William H. ;

Koch, Wayne M. ;

Califano, Joseph A. ;

Gibbs, Richard A. ;

Sidransky, David ;

Vogelstein, Bert ;

Velculescu, Victor E. ;

Papadopoulos, Nickolas ;

Wheeler, David A. ;

Kinzler, Kenneth W. ;

Myers, Jeffrey N. .

SCIENCE, 2011, 333 (6046) :1154-1157

[4] Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non-adenoid cystic carcinoma malignant tumors of the salivary glands [J].

Agulnik, Mark ;

Cohen, Ezra W. E. ;

Cohen, Roger B. ;

Chen, Eric X. ;

Vokes, Everett E. ;

Hotte, Sebastien J. ;

Winquist, Eric ;

Laurie, Scott ;

Hayes, D. Neil ;

Dancey, Janet E. ;

Brown, Shirley ;

Pond, Gregory R. ;

Lorimer, Ian ;

Daneshmand, Manijeh ;

Ho, James ;

Tsao, Ming-Sound ;

Siu, Lillian L. .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (25) :3978-3984

[5] Activated Notch1 Induces Lung Adenomas in Mice and Cooperates with Myc in the Generation of Lung Adenocarcinoma [J].

Allen, Thaddeus D. ;

Rodriguez, Elena M. ;

Jones, Kirk D. ;

Bishop, J. Michael .

CANCER RESEARCH, 2011, 71 (18) :6010-6018

[6] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[7] Gene Ontology: tool for the unification of biology [J].

Ashburner, M ;

Ball, CA ;

Blake, JA ;

Botstein, D ;

Butler, H ;

Cherry, JM ;

Davis, AP ;

Dolinski, K ;

Dwight, SS ;

Eppig, JT ;

Harris, MA ;

Hill, DP ;

Issel-Tarver, L ;

Kasarskis, A ;

Lewis, S ;

Matese, JC ;

Richardson, JE ;

Ringwald, M ;

Rubin, GM ;

Sherlock, G .

NATURE GENETICS, 2000, 25 (01) :25-29

[8] Sequence analysis of mutations and translocations across breast cancer subtypes [J].

Banerji, Shantanu ;

Cibulskis, Kristian ;

Rangel-Escareno, Claudia ;

Brown, Kristin K. ;

Carter, Scott L. ;

Frederick, Abbie M. ;

Lawrence, Michael S. ;

Sivachenko, Andrey Y. ;

Sougnez, Carrie ;

Zou, Lihua ;

Cortes, Maria L. ;

Fernandez-Lopez, Juan C. ;

Peng, Shouyong ;

Ardlie, Kristin G. ;

Auclair, Daniel ;

Bautista-Pina, Veronica ;

Duke, Fujiko ;

Francis, Joshua ;

Jung, Joonil ;

Maffuz-Aziz, Antonio ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Pho, Nam H. ;

Quintanar-Jurado, Valeria ;

Ramos, Alex H. ;

Rebollar-Vega, Rosa ;

Rodriguez-Cuevas, Sergio ;

Romero-Cordoba, Sandra L. ;

Schumacher, Steven E. ;

Stransky, Nicolas ;

Thompson, Kristin M. ;

Uribe-Figueroa, Laura ;

Baselga, Jose ;

Beroukhim, Rameen ;

Polyak, Kornelia ;

Sgroi, Dennis C. ;

Richardson, Andrea L. ;

Jimenez-Sanchez, Gerardo ;

Lander, Eric S. ;

Gabriel, Stacey B. ;

Garraway, Levi A. ;

Golub, Todd R. ;

Melendez-Zajgla, Jorge ;

Toker, Alex ;

Getz, Gad ;

Hidalgo-Miranda, Alfredo ;

Meyerson, Matthew .

NATURE, 2012, 486 (7403) :405-409

[9] The CBP co-activator is a histone acetyltransferase [J].

Bannister, AJ ;

Kouzarides, T .

NATURE, 1996, 384 (6610) :641-643

[10] Estimation and assessment of raw copy numbers at the single locus level [J].

Bengtsson, H. ;

Irizarry, R. ;

Carvalho, B. ;

Speed, T. P. .

BIOINFORMATICS, 2008, 24 (06) :759-767

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