The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

被引：1920

作者：

Stransky, Nicolas ^{[1
]}

Egloff, Ann Marie ^{[2
,3
]}

Tward, Aaron D. ^{[1
,4
,5
]}

Kostic, Aleksandar D. ^{[1
,6
]}

Cibulskis, Kristian ^{[1
]}

Sivachenko, Andrey ^{[1
]}

Kryukov, Gregory V. ^{[1
,6
]}

Lawrence, Michael S. ^{[1
]}

Sougnez, Carrie ^{[1
]}

McKenna, Aaron ^{[1
]}

Shefler, Erica ^{[1
]}

Ramos, Alex H. ^{[1
]}

Stojanov, Petar ^{[1
]}

Carter, Scott L. ^{[1
]}

Voet, Douglas ^{[1
]}

Cortes, Maria L. ^{[1
]}

Auclair, Daniel ^{[1
]}

Berger, Michael F. ^{[1
]}

Saksena, Gordon ^{[1
]}

Guiducci, Candace ^{[1
]}

Onofrio, Robert C. ^{[1
]}

Parkin, Melissa ^{[1
]}

Romkes, Marjorie ^{[7
,8
]}

Weissfeld, Joel L. ^{[9
,10
]}

Seethala, Raja R. ^{[3
,11
]}

Wang, Lin ^{[3
,11
]}

Rangel-Escareno, Claudia ^{[12
]}

Carlos Fernandez-Lopez, Juan ^{[12
]}

Hidalgo-Miranda, Alfredo ^{[12
]}

Melendez-Zajgla, Jorge ^{[12
]}

Winckler, Wendy ^{[1
]}

Ardlie, Kristin ^{[1
]}

Gabriel, Stacey B. ^{[1
]}

Meyerson, Matthew ^{[1
,6
,13
,14
]}

Lander, Eric S. ^{[1
,6
,15
]}

Getz, Gad ^{[1
]}

Golub, Todd R. ^{[1
,6
,14
,16
,17
]}

Garraway, Levi A. ^{[1
,6
,13
,14
]}

Grandis, Jennifer R. ^{[2
,3
,18
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA

[3] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA

[4] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA

[5] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA

[6] Harvard Univ, Sch Med, Boston, MA 02115 USA

[7] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA

[8] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA

[9] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15232 USA

[10] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA

[11] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA

[12] Inst Nacl Med Genom, Mexico City 01900, DF, Mexico

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

[14] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[15] MIT, Cambridge, MA 02142 USA

[16] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[17] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[18] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA

来源：

SCIENCE | 2011年 / 333卷 / 6046期

关键词：

TUMOR-SUPPRESSOR; STEM-CELLS; E-CADHERIN; CANCER; NOTCH; SKIN; DIFFERENTIATION; GENOME; KERATINOCYTES; INACTIVATION;

D O I：

10.1126/science.1208130

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.

引用

页码：1157 / 1160

页数：4

共 33 条

[1] Head and neck cancer
Argiris, Athanassios
Karamouzis, Michalis V.
Raben, David
Ferris, Robert L.
[J]. LANCET, 2008, 371 (9625) : 1695 - 1709
[2] Integrated genomic analyses of ovarian carcinoma
Bell, D.
Berchuck, A.
Birrer, M.
Chien, J.
Cramer, D. W.
Dao, F.
Dhir, R.
DiSaia, P.
Gabra, H.
Glenn, P.
Godwin, A. K.
Gross, J.
Hartmann, L.
Huang, M.
Huntsman, D. G.
Iacocca, M.
Imielinski, M.
Kalloger, S.
Karlan, B. Y.
Levine, D. A.
Mills, G. B.
Morrison, C.
Mutch, D.
Olvera, N.
Orsulic, S.
Park, K.
Petrelli, N.
Rabeno, B.
Rader, J. S.
Sikic, B. I.
Smith-McCune, K.
Sood, A. K.
Bowtell, D.
Penny, R.
Testa, J. R.
Chang, K.
Dinh, H. H.
Drummond, J. A.
Fowler, G.
Gunaratne, P.
Hawes, A. C.
Kovar, C. L.
Lewis, L. R.
Morgan, M. B.
Newsham, I. F.
Santibanez, J.
Reid, J. G.
Trevino, L. R.
Wu, Y. -Q.
Wang, M.
[J]. NATURE, 2011, 474 (7353) : 609 - 615
[3] Epidermal homeostasis: a balancing act of stem cells in the skin
Blanpain, Cedric
Fuchs, Elaine
[J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (03) : 207 - U67
[4] Initial genome sequencing and analysis of multiple myeloma
Chapman, Michael A.
Lawrence, Michael S.
Keats, Jonathan J.
Cibulskis, Kristian
Sougnez, Carrie
Schinzel, Anna C.
Harview, Christina L.
Brunet, Jean-Philippe
Ahmann, Gregory J.
Adli, Mazhar
Anderson, Kenneth C.
Ardlie, Kristin G.
Auclair, Daniel
Baker, Angela
Bergsagel, P. Leif
Bernstein, Bradley E.
Drier, Yotam
Fonseca, Rafael
Gabriel, Stacey B.
Hofmeister, Craig C.
Jagannath, Sundar
Jakubowiak, Andrzej J.
Krishnan, Amrita
Levy, Joan
Liefeld, Ted
Lonial, Sagar
Mahan, Scott
Mfuko, Bunmi
Monti, Stefano
Perkins, Louise M.
Onofrio, Robb
Pugh, Trevor J.
Rajkumar, S. Vincent
Ramos, Alex H.
Siegel, David S.
Sivachenko, Andrey
Stewart, A. Keith
Trudel, Suzanne
Vij, Ravi
Voet, Douglas
Winckler, Wendy
Zimmerman, Todd
Carpten, John
Trent, Jeff
Hahn, William C.
Garraway, Levi A.
Meyerson, Matthew
Lander, Eric S.
Getz, Gad
Golub, Todd R.
[J]. NATURE, 2011, 471 (7339) : 467 - 472
[5] Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation
Chidgey, M
Brakebusch, C
Gustafsson, E
Cruchley, A
Hail, C
Kirk, S
Merritt, A
North, A
Tselepis, C
Hewitt, J
Byrne, C
Fassler, R
Garrod, D
[J]. JOURNAL OF CELL BIOLOGY, 2001, 155 (05) : 821 - 832
[6] Atopic Dermatitis-Like Disease and Associated Lethal Myeloproliferative Disorder Arise from Loss of Notch Signaling in the Murine Skin
Dumortier, Alexis
Durham, Andre-Dante
Di Piazza, Matteo
Vauclair, Sophie
Koch, Ute
Ferrand, Gisele
Ferrero, Isabel
Demehri, Shadmehr
Song, Lynda Li
Farr, Andrew G.
Leonard, Warren J.
Kopan, Raphael
Miele, Lucio
Hohl, Daniel
Finke, Daniela
Radtke, Freddy
[J]. PLOS ONE, 2010, 5 (02):
[7] Alzheimer's failure raises questions about disease-modifying strategies
Extance, Andy
[J]. NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (10) : 749 - U87
[8] EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair
Ezhkova, Elena
Lien, Wen-Hui
Stokes, Nicole
Pasolli, H. Amalia
Silva, Jose M.
Fuchs, Elaine
[J]. GENES & DEVELOPMENT, 2011, 25 (05) : 485 - 498
[9] Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008
Ferlay, Jacques
Shin, Hai-Rim
Bray, Freddie
Forman, David
Mathers, Colin
Parkin, Donald Maxwell
[J]. INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) : 2893 - 2917
[10] Piccolo, a Ca2+ sensor in pancreatic β-cells -: Involvement of cAMP-GEFII•Rim2•Piccolo complex in cAMP-dependent exocytosis
Fujimoto, K
Shibasaki, T
Yokoi, N
Kashima, Y
Matsumoto, M
Sasaki, T
Tajima, N
Iwanaga, T
Seino, S
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (52) : 50497 - 50502

← 1 2 3 4 →