Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

被引：250

作者：

Campbell, Joshua D. ^{[1
,2
,3
,4
]}

Yau, Christina ^{[5
]}

Bowlby, Reanne ^{[6
]}

Liu, Yuexin ^{[7
]}

Brennan, Kevin ^{[8
]}

Fan, Huihui ^{[9
]}

Taylor, Alison M. ^{[1
,2
,3
]}

Wang, Chen ^{[10
]}

Walter, Vonn ^{[11
,12
]}

Akbani, Rehan ^{[7
]}

Byers, Lauren Averett ^{[7
,13
]}

Creighton, Chad J. ^{[7
,14
,15
]}

Coarfa, Cristian ^{[16
]}

Shih, Juliann ^{[1
,2
,3
]}

Cherniack, Andrew D. ^{[1
,2
,3
]}

Gevaert, Olivier ^{[8
]}

Prunello, Marcos ^{[8
]}

Shen, Hui ^{[9
]}

Anur, Pavana ^{[17
]}

Chen, Jianhong ^{[18
]}

Cheng, Hui ^{[18
]}

Hayes, D. Neil ^{[12
]}

Bullman, Susan ^{[1
,2
,3
]}

Pedamallu, Chandra Sekhar ^{[1
,2
,3
]}

Ojesina, Akinyemi I. ^{[19
,20
]}

Sadeghi, Sara ^{[6
]}

Mungall, Karen L. ^{[6
]}

Robertson, A. Gordon ^{[6
]}

Benz, Christopher ^{[5
]}

Schultz, Andre ^{[7
]}

Kanchi, Rupa S. ^{[7
]}

Gay, Carl M. ^{[13
]}

Hegde, Apurva ^{[7
]}

Diao, Lixia ^{[7
]}

Wang, Jing ^{[7
]}

Ma, Wencai ^{[7
]}

Sumazin, Pavel ^{[21
]}

Chiu, Hua-Sheng ^{[21
]}

Chen, Ting-Wen ^{[21
]}

Gunaratne, Preethi ^{[22
,23
]}

Donehower, Larry ^{[24
]}

Rader, Janet S. ^{[25
]}

Zuna, Rosemary ^{[26
]}

Al-Ahmadie, Hikmat ^{[27
]}

Lazar, Alexander J. ^{[28
,29
,30
,31
]}

Flores, Elsa R. ^{[32
]}

Tsai, Kenneth Y. ^{[33
,34
]}

Zhou, Jane H. ^{[35
]}

Rustgi, Anil K. ^{[36
,37
]}

Drill, Esther ^{[38
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA

[3] Harvard Univ, Cambridge, MA 02142 USA

[4] Boston Univ, Sch Med, Boston, MA 02118 USA

[5] Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94945 USA

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

[7] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[8] Stanford Univ, Dept Med Biomed Informat Res, Stanford, CA 94305 USA

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

[10] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA

[11] Penn State Milton Hershey Med Ctr, Dept Publ Hlth Sci, Hershey, PA 17033 USA

[12] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

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

[14] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

[15] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Div Biostat, Houston, TX 77030 USA

[16] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA

[17] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA

[18] NIH, Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD 20892 USA

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

[20] Hudson Alpha Inst Biotechnol, Huntsville, AL 35806 USA

[21] Baylor Coll Med, Texas Childrens Canc Ctr, Dept Med Pediat, Houston, TX 77030 USA

[22] Univ Houston, UH SeqNEdit Core, Dept Biol & Biochem, Houston, TX 77204 USA

[23] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[24] Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA

[25] Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA

[26] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA

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

[28] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77401 USA

[29] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77401 USA

[30] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77401 USA

[31] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77401 USA

[32] H Lee Moffitt Canc Ctr & Res Inst, Mol Oncol, Tampa, FL 33612 USA

[33] H Lee Moffitt Canc Ctr & Res Inst, Dept Anat Pathol, Tampa, FL 33612 USA

[34] H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, Tampa, FL 33612 USA

[35] Roswell Pk Comprehens Canc Ctr, Dept Pathol, Buffalo, NY 14263 USA

[36] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Div Gastroenterol,Dept Med, Philadelphia, PA 19104 USA

[37] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Genet, Philadelphia, PA 19104 USA

[38] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA

[39] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[40] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[41] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA

来源：

CELL REPORTS | 2018年 / 23卷 / 01期

关键词：

CELL CARCINOMA; FANCONI-ANEMIA; ANTITUMOR-ACTIVITY; HUMAN HEAD; INHIBITOR; EXPRESSION; PHOSPHORYLATION; PROTEINS; CANCERS; GENES;

D O I：

10.1016/j.celrep.2018.03.063

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the Delta Np63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

引用

页码：194 / +

页数：25

共 80 条

[1] Functional Genetic Screen Identifies Increased Sensitivity to WEE1 Inhibition in Cells with Defects in Fanconi Anemia and HR Pathways [J].

Aarts, Marieke ;

Bajrami, Ilirjana ;

Herrera-Abreu, Maria T. ;

Elliott, Richard ;

Brough, Rachel ;

Ashworth, Alan ;

Lord, Christopher J. ;

Turner, Nicholas C. .

MOLECULAR CANCER THERAPEUTICS, 2015, 14 (04) :865-876

[2] Squamous cell carcinomas in patients with Fanconi anemia and dyskeratosis congenita: A search for human papillomavirus [J].

Alter, Blanche P. ;

Giri, Neelam ;

Savage, Sharon A. ;

Quint, Wim G. V. ;

de Koning, Maurits N. C. ;

Schiffman, Mark .

INTERNATIONAL JOURNAL OF CANCER, 2013, 133 (06) :1513-1515

[3] TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer [J].

Banerjee, Rajat ;

Russo, Nickole ;

Liu, Min ;

Basrur, Venkatesha ;

Bellile, Emily ;

Palanisamy, Nallasivam ;

Scanlon, Christina S. ;

van Tubergen, Elizabeth ;

Inglehart, Ronald C. ;

Metwally, Tarek ;

Mani, Ram-Shankar ;

Yocum, Anastasia ;

Nyati, Mukesh K. ;

Castilho, Rogerio M. ;

Varambally, Sooryanarayana ;

Chinnaiyan, Arul M. ;

D'Silva, Nisha J. .

NATURE COMMUNICATIONS, 2014, 5

[4] ΔNp63α expression is regulated by the phosphoinositide 3-kinase pathway [J].

Barbieri, CE ;

Barton, CE ;

Pietenpol, JA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (51) :51408-51414

[5] A Galaxy Implementation of Next-Generation Clustered Heatmaps for Interactive Exploration of Molecular Profiling Data [J].

Broom, Bradley M. ;

Ryan, Michael C. ;

Brown, Robert E. ;

Ikeda, Futa ;

Stucky, Mark ;

Kane, David W. ;

Melott, James ;

Wakefield, Chris ;

Casasent, Tod D. ;

Akbani, Rehan ;

Weinstein, John N. .

CANCER RESEARCH, 2017, 77 (21) :E23-E26

[6] Principles of microRNA Regulation Revealed Through Modeling microRNA Expression Quantitative Trait Loci [J].

Budach, Stefan ;

Heinig, Matthias ;

Marsico, Annalisa .

GENETICS, 2016, 203 (04) :1629-+

[7] Integrated genomic and molecular characterization of cervical cancer [J].

Burk, Robert D. ;

Chen, Zigui ;

Saller, Charles ;

Tarvin, Katherine ;

Carvalho, Andre L. ;

Scapulatempo-Neto, Cristovam ;

Silveira, Henrique C. ;

Fregnani, Jose H. ;

Creighton, Chad J. ;

Anderson, Matthew L. ;

Castro, Patricia ;

Wang, Sophia S. ;

Yau, Christina ;

Benz, Christopher ;

Robertson, A. Gordon ;

Mungall, Karen ;

Lim, Lynette ;

Bowlby, Reanne ;

Sadeghi, Sara ;

Brooks, Denise ;

Sipahimalani, Payal ;

Mar, Richard ;

Ally, Adrian ;

Clarke, Amanda ;

Mungall, Andrew J. ;

Tam, Angela ;

Lee, Darlene ;

Chuah, Eric ;

Schein, Jacqueline E. ;

Tse, Kane ;

Kasaian, Katayoon ;

Ma, Yussanne ;

Marra, Marco A. ;

Mayo, Michael ;

Balasundaram, Miruna ;

Thiessen, Nina ;

Dhalla, Noreen ;

Carlsen, Rebecca ;

Moore, Richard A. ;

Holt, Robert A. ;

Jones, Steven J. M. ;

Wong, Tina ;

Pantazi, Angeliki ;

Parfenov, Michael ;

Kucherlapati, Raju ;

Hadjipanayis, Angela ;

Seidman, Jonathan ;

Kucherlapati, Melanie ;

Ren, Xiaojia ;

Xu, Andrew W. .

NATURE, 2017, 543 (7645) :378-+

[8] Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas [J].

Campbell, Joshua D. ;

Alexandrov, Anton ;

Kim, Jaegil ;

Wala, Jeremiah ;

Berger, Alice H. ;

Pedamallu, Chandra Sekhar ;

Shukla, Sachet A. ;

Guo, Guangwu ;

Brooks, Angela N. ;

Murray, Bradley A. ;

Imielinski, Marcin ;

Hu, Xin ;

Ling, Shiyun ;

Akbani, Rehan ;

Rosenberg, Mara ;

Cibulskis, Carrie ;

Ramachandran, Aruna ;

Collisson, Eric A. ;

Kwiatkowski, David J. ;

Lawrence, Michael S. ;

Weinstein, John N. ;

Verhaak, Roel G. W. ;

Wu, Catherine J. ;

Hammerman, Peter S. ;

Cherniack, Andrew D. ;

Getz, Gad ;

Artyomov, Maxim N. ;

Schreiber, Robert ;

Govindan, Ramaswamy ;

Meyerson, Matthew .

NATURE GENETICS, 2016, 48 (06) :607-+

[9] The Fanconi anaemia pathway: newyplayers and new functions [J].

Ceccaldi, Raphael ;

Sarangi, Prabha ;

D'Andrea, Alan D. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2016, 17 (06) :337-349

[10] Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade [J].

Charoentong, Pornpimol ;

Finotello, Francesca ;

Angelova, Mihaela ;

Mayer, Clemens ;

Efremova, Mirjana ;

Rieder, Dietmar ;

Hackl, Hubert ;

Trajanoski, Zlatko .

CELL REPORTS, 2017, 18 (01) :248-262

← 1 2 3 4 5 6 7 8 →