Whole exome sequencing of adenoid cystic carcinoma

被引：221

作者：

Stephens, Philip J. ^{[1
]}

Davies, Helen R. ^{[1
]}

Mitani, Yoshitsugu ^{[2
]}

Van Loo, Peter ^{[1
,3
,4
]}

Shlien, Adam ^{[1
]}

Tarpey, Patrick S. ^{[1
]}

Papaemmanuil, Elli ^{[1
]}

Cheverton, Angela ^{[1
]}

Bignell, Graham R. ^{[1
]}

Butler, Adam R. ^{[1
]}

Gamble, John ^{[1
]}

Gamble, Stephen ^{[1
]}

Hardy, Claire ^{[1
]}

Hinton, Jonathan ^{[1
]}

Jia, Mingming ^{[1
]}

Jayakuniar, Alagu ^{[1
]}

Jones, David ^{[1
]}

Latimer, Calli ^{[1
]}

McLaren, Stuart ^{[1
]}

McBride, David J. ^{[1
]}

Menzies, Andrew ^{[1
]}

Mudie, Laura ^{[1
]}

Maddison, Mark ^{[1
]}

Raine, Keiran ^{[1
]}

Nik-Zainal, Serena ^{[1
]}

O'Meara, Sarah ^{[1
]}

Teague, Jon W. ^{[1
]}

Varela, Ignacio ^{[1
]}

Wedge, David C. ^{[1
]}

Whitmore, Ian ^{[1
]}

Lippman, Scott M. ^{[5
]}

McDermott, Ultan ^{[1
]}

Stratton, Michael R. ^{[1
]}

Campbell, Peter J. ^{[1
]}

El-Naggar, Adel K. ^{[2
]}

Futreal, P. Andrew ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, Cambs, England

[2] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[3] VIB, Dept Human Genet, Human Genome Lab, Louvain, Belgium

[4] Katholieke Univ Leuven, Louvain, Belgium

[5] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2013年 / 123卷 / 07期

基金：

英国惠康基金;

关键词：

IDENTIFIES FREQUENT MUTATION; SQUAMOUS-CELL CARCINOMA; INACTIVATING MUTATIONS; GENETIC LANDSCAPE; CANCER; HEAD; NECK; NFIB; MYB; REARRANGEMENTS;

D O I：

10.1172/JCI67201

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.

引用

页码：2965 / 2968

页数：4

共 26 条

[1] 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

[2]

[Anonymous], CAT SOM MUT CANC

[3]

Bhayani MK, 2011, CANCER, V118, P2872

[4] FGFR2 mutations are rare across histologic subtypes of ovarian cancer [J].

Byron, Sara A. ;

Gartside, Michael G. ;

Wellens, Candice L. ;

Goodfellow, Paul J. ;

Birrer, Michael J. ;

Campbell, Ian G. ;

Pollock, Pamela M. .

GYNECOLOGIC ONCOLOGY, 2010, 117 (01) :125-129

[5] Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder [J].

Gui, Yaoting ;

Guo, Guangwu ;

Huang, Yi ;

Hu, Xueda ;

Tang, Aifa ;

Gao, Shengjie ;

Wu, Renhua ;

Chen, Chao ;

Li, Xianxin ;

Zhou, Liang ;

He, Minghui ;

Li, Zesong ;

Sun, Xiaojuan ;

Jia, Wenlong ;

Chen, Jinnong ;

Yang, Shangming ;

Zhou, Fangjian ;

Zhao, Xiaokun ;

Wan, Shengqing ;

Ye, Rui ;

Liang, Chaozhao ;

Liu, Zhisheng ;

Huang, Peide ;

Liu, Chunxiao ;

Jiang, Hui ;

Wang, Yong ;

Zheng, Hancheng ;

Sun, Liang ;

Liu, Xingwang ;

Jiang, Zhimao ;

Feng, Dafei ;

Chen, Jing ;

Wu, Song ;

Zou, Jing ;

Zhang, Zhongfu ;

Yang, Ruilin ;

Zhao, Jun ;

Xu, Congjie ;

Yin, Weihua ;

Guan, Zhichen ;

Ye, Jiongxian ;

Zhang, Hong ;

Li, Jingxiang ;

Kristiansen, Karsten ;

Nickerson, Michael L. ;

Theodorescu, Dan ;

Li, Yingrui ;

Zhang, Xiuqing ;

Li, Songgang ;

Wang, Jian .

NATURE GENETICS, 2011, 43 (09) :875-878

[6] The C terminus of MINT forms homodimers and abrogates MINT-mediated transcriptional repression [J].

Li, JL ;

Li, JF ;

Yang, X ;

Qin, HY ;

Zhou, P ;

Liang, YM ;

Han, H .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2005, 1729 (01) :50-56

[7] Novel Chromosomal Rearrangements and Break Points at the t(6;9) in Salivary Adenoid Cystic Carcinoma: Association with MYB-NFIB Chimeric Fusion, MYB Expression, and Clinical Outcome [J].

Mitani, Yoshitsugu ;

Rao, Pulivarthi H. ;

Futreal, P. Andrew ;

Roberts, Dianna B. ;

Stephens, Philip J. ;

Zhao, Yi-Jue ;

Zhang, Li ;

Mitani, Mutsumi ;

Weber, Randal S. ;

Lippman, Scott M. ;

Caulin, Carlos ;

El-Naggar, Adel K. .

CLINICAL CANCER RESEARCH, 2011, 17 (22) :7003-7014

[8] SHARP is a novel component of the Notch/RBP-Jκ signalling pathway [J].

Oswald, F ;

Kostezka, U ;

Astrahantseff, K ;

Bourteele, S ;

Dillinger, K ;

Zechner, U ;

Ludwig, L ;

Wilda, M ;

Hameister, H ;

Knöchel, W ;

Liptay, S ;

Schmid, RM .

EMBO JOURNAL, 2002, 21 (20) :5417-5426

[9] Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts [J].

Papaemmanuil, E. ;

Cazzola, M. ;

Boultwood, J. ;

Malcovati, L. ;

Vyas, P. ;

Bowen, D. ;

Pellagatti, A. ;

Wainscoat, J. S. ;

Hellstrom-Lindberg, E. ;

Gambacorti-Passerini, C. ;

Godfrey, A. L. ;

Rapado, I. ;

Cvejic, A. ;

Rance, R. ;

McGee, C. ;

Ellis, P. ;

Mudie, L. J. ;

Stephens, P. J. ;

McLaren, S. ;

Massie, C. E. ;

Tarpey, P. S. ;

Varela, I. ;

Nik-Zainal, S. ;

Davies, H. R. ;

Shlien, A. ;

Jones, D. ;

Raine, K. ;

Hinton, J. ;

Butler, A. P. ;

Teague, J. W. ;

Baxter, E. J. ;

Score, J. ;

Galli, A. ;

Della Porta, M. G. ;

Travaglino, E. ;

Groves, M. ;

Tauro, S. ;

Munshi, N. C. ;

Anderson, K. C. ;

El-Naggar, A. ;

Fischer, A. ;

Mustonen, V. ;

Warren, A. J. ;

Cross, N. C. P. ;

Green, A. R. ;

Futreal, P. A. ;

Stratton, M. R. ;

Campbell, P. J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (15) :1384-1395

[10] The Genetic Landscape of the Childhood Cancer Medulloblastoma [J].

Parsons, D. Williams ;

Li, Meng ;

Zhang, Xiaosong ;

Jones, Sian ;

Leary, Rebecca J. ;

Lin, Jimmy Cheng-Ho ;

Boca, Simina M. ;

Carter, Hannah ;

Samayoa, Josue ;

Bettegowda, Chetan ;

Gallia, Gary L. ;

Jallo, George I. ;

Binder, Zev A. ;

Nikolsky, Yuri ;

Hartigan, James ;

Smith, Doug R. ;

Gerhard, Daniela S. ;

Fults, Daniel W. ;

VandenBerg, Scott ;

Berger, Mitchel S. ;

Marie, Suely Kazue Nagahashi ;

Shinjo, Sueli Mieko Oba ;

Clara, Carlos ;

Phillips, Peter C. ;

Minturn, Jane E. ;

Biegel, Jaclyn A. ;

Judkins, Alexander R. ;

Resnick, Adam C. ;

Storm, Phillip B. ;

Curran, Tom ;

He, Yiping ;

Rasheed, B. Ahmed ;

Friedman, Henry S. ;

Keir, Stephen T. ;

McLendon, Roger ;

Northcott, Paul A. ;

Taylor, Michael D. ;

Burger, Peter C. ;

Riggins, Gregory J. ;

Karchin, Rachel ;

Parmigiani, Giovanni ;

Bigner, Darell D. ;

Yan, Hai ;

Papadopoulos, Nick ;

Vogelstein, Bert ;

Kinzler, Kenneth W. ;

Velculescu, Victor E. .

SCIENCE, 2011, 331 (6016) :435-439

← 1 2 3 →