The head and neck cancer cell oncogenome: A platform for the development of precision molecular therapies

Oncotarget

Volumn 5, Issue 19, 2014, Pages 8906-8923

  Martin, Daniel ^a   Abba, Martin C ^b   Molinolo, Alfredo A ^a   Vitale Cross, Lynn ^a   Wang, Zhiyong ^a   Zaida, Moraima ^a   Delic, Naomi C ^d,e   Samuels, Yardena ^c   Lyons, J Guy ^d,e   Gutkind, J Silvio ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b FACULTAD DE CIENCIAS MÉDICAS   (Argentina)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^d UNIVERSITY OF SYDNEY   (Australia)

^e ROYAL PRINCE ALFRED HOSPITAL   (Australia)

Author keywords

Cancer; Exome; HNSCC; RNAseq; Sequencing

Indexed keywords

PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SMAD4 PROTEIN; TRANSCRIPTOME; CADHERIN; CASP8 PROTEIN, HUMAN; CASPASE 8; CDK2 PROTEIN, HUMAN; CYCLIN DEPENDENT KINASE 2; FAT1 PROTEIN, HUMAN; HRAS PROTEIN, HUMAN; MTOR PROTEIN, HUMAN; NOTCH1 PROTEIN, HUMAN; NOTCH1 RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PIK3CA PROTEIN, HUMAN; PROTEIN P21; PROTEIN P53; PTEN PROTEIN, HUMAN; SMAD4 PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE; TP53 PROTEIN, HUMAN; TRANSFORMING GROWTH FACTOR BETA;

ARTICLE; CANCER CELL; CCDN1 GENE; CDKN2A GENE; CELL PROLIFERATION; COPY NUMBER VARIATION; EGFR GENE; EPHA2 GENE; EXOME; GENE AMPLIFICATION; GENE DELETION; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; GENETIC VARIABILITY; HEAD AND NECK CANCER; HEMIZYGOSITY; HOMOZYGOSITY; HUMAN; HUMAN CELL; KDM6A GENE; KEAP1 GENE; KERATINOCYTE; NFE2L2 GENE; NOTCH1 GENE; ONCOGENE; PIK3CA GENE; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN PHOSPHORYLATION; PTEN GENE; SMAD4 GENE; SOMATIC MUTATION; TGF BETA GENE; TP53 GENE; BIOSYNTHESIS; DNA SEQUENCE; GENE DOSAGE; GENE EXPRESSION PROFILING; GENETICS; HEAD AND NECK TUMOR; METABOLISM; NUCLEOTIDE SEQUENCE; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTION; PERSONALIZED MEDICINE; SQUAMOUS CELL CARCINOMA; TUMOR CELL LINE;

BASE SEQUENCE; CADHERINS; CARCINOMA, SQUAMOUS CELL; CASPASE 8; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE 2; DNA COPY NUMBER VARIATIONS; GENE DOSAGE; GENE EXPRESSION PROFILING; HEAD AND NECK NEOPLASMS; HUMANS; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTIONS; PHOSPHATIDYLINOSITOL 3-KINASES; PRECISION MEDICINE; PROTO-ONCOGENE PROTEINS P21(RAS); PTEN PHOSPHOHYDROLASE; RECEPTOR, NOTCH1; SEQUENCE ANALYSIS, DNA; SMAD4 PROTEIN; TOR SERINE-THREONINE KINASES; TRANSCRIPTOME; TRANSFORMING GROWTH FACTOR BETA; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84910064929     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2417     Document Type: Article

References (83)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014; 64:9-29.
2. Warnakulasuriya S. Causes of oral cancer-an appraisal of controversies. Br Dent J. 2009; 207:471-475.
3. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, etal. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29:4294-4301.
4. Chung CH, Gillison ML. Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res. 2009; 15:6758-6762.
5. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011; 11:9-22.
6. Zhao M, Sano D, Pickering CR, Jasser SA, HendersonYC, Clayman GL, Sturgis EM, Ow TJ, Lotan R, Carey TE, SacksPG, Grandis JR, Sidransky D, Heldin NE, MyersJN. Assembly and initial characterization of a panel of 85genomically validated cell lines from diverse head and neck tumor sites. Clin Cancer Res. 2011; 17:7248-7264.
7. Sano D, Myers JN. Xenograft models of head and neck cancers. Head Neck Oncol. 2009; 1:32.
8. Patel V, Marsh CA, Dorsam RT, Mikelis CM, MasedunskasA, Amornphimoltham P, Nathan CA, SinghB, Weigert R, Molinolo AA, Gutkind JS. Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer. Cancer Res. 2011; 71:7103-7112.
9. Stransky N, Egloff AM, Tward AD, Kostic AD, CibulskisK, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, StojanovP, Carter SL, Voet D, Cortes ML, etal. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011; 333:1157-1160.
10. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang JX, Wang J, Zhang NX, El-Naggar AK, Jasser SA, Weinstein JN, TrevinoL, Drummond JA, etal. Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1. Science. 2011; 333:1154-1157.
11. Lui VW, Hedberg ML, Li H, Vangara BS, Pendleton K, Zeng Y, Lu Y, Zhang Q, Du Y, Gilbert BR, Freilino M, Sauerwein S, Peyser ND, Xiao D, Diergaarde B, Wang L, etal. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 2013; 3:761-769.
12. Pickering CR, Zhang J, Yoo SY, Bengtsson L, MoorthyS, Neskey DM, Zhao M, Ortega Alves MV, Chang K, Drummond J, Cortez E, Xie TX, Zhang D, Chung W, IssaJP, Zweidler-McKay PA, etal. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov. 2013; 3:770-781.
13. Molinolo AA, Marsh C, El Dinali M, Gangane N, JennisonK, Hewitt S, Patel V, Seiwert TY, Gutkind JS. mTOR as a molecular target in HPV-associated oral and cervical squamous carcinomas. Clin Cancer Res. 2012; 18:2558-2568.
14. Wellcome Trust Sanger Institute. COSMIC Cell Lines Project. http://cancer.sanger.ac.uk/cancergenome/projects/cell_lines/about
15. National Heart, Lung and Blood Institute. National Institutes of Health. NHLBI/ESP6500 Exome Sequencing Project (ESP). http://evs.gs.washington.edu/EVS/
16. Forbes SA, Bhamra G, Bamford S, Dawson E, Kok C, Clements J, Menzies A, Teague JW, Futreal PA, Stratton MR. The Catalogue of Somatic Mutations in Cancer (COSMIC). Curr Protoc Hum Genet. 2008; Chapter 10: Unit 10 11.
17. Poeta ML, Manola J, Goldwasser MA, Forastiere A, BenoitN, Califano JA, Ridge JA, Goodwin J, KenadyD, Saunders J, Westra W, Sidransky D, Koch WM. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 2007; 357: 2552-2561.
18. Sano D, Xie TX, Ow TJ, Zhao M, Pickering CR, ZhouG, Sandulache VC, Wheeler DA, Gibbs RA, Caulin C, Myers JN. Disruptive TP53 mutation is associated with aggressive disease characteristics in an orthotopic murine model of oral tongue cancer. Clin Cancer Res. 2011; 17: 6658-6670.
19. Iglesias-Bartolome R, Martin D, Gutkind JS. Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets. Cancer Discov. 2013; 3:722-725.
20. Amornphimoltham P, Patel V, Sodhi A, Nikitakis NG, SaukJJ, Sausville EA, Molinolo AA, Gutkind JS. Mammalian Target of Rapamycin, a Molecular Target in Squamous Cell Carcinomas of the Head and Neck. Cancer Res. 2005; 65:9953-9961.
21. Molinolo AA, Hewitt SM, Amornphimoltham P, KeelawatS, Rangdaeng S, Meneses Garcia A, RaimondiAR, Jufe R, ItoizM, Gao Y, Saranath D, Kaleebi GS, Yoo GH, LeakL, Myers EM, Shintani S, etal. Dissecting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative. Clin Cancer Res. 2007; 13:4964-4973.
22. Morris LG, Kaufman AM, Gong Y, Ramaswami D, WalshLA, Turcan S, Eng S, Kannan K, Zou Y, PengL, Banuchi VE, Paty P, Zeng Z, Vakiani E, Solit D, SinghB, etal. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat Genet. 2013; 45:253-261.
23. Nishikawa Y, Miyazaki T, Nakashiro K, Yamagata H, Isokane M, Goda H, Tanaka H, Oka R, Hamakawa H. Human FAT1 cadherin controls cell migration and invasion of oral squamous cell carcinoma through the localization of beta-catenin. Oncol Rep. 2011; 26:587-592.
24. Sun W, Gaykalova DA, Ochs MF, Mambo E, ArnaoutakisD, Liu Y, Loyo M, Agrawal N, Howard J, LiR, Ahn S, Fertig E, Sidransky D, Houghton J, Buddavarapu K, Sanford T, etal. Activation of the NOTCH pathway in head and neck cancer. Cancer Res. 2014; 74:1091-1104.
25. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003; 114:181-190.
26. Ando M, Kawazu M, Ueno T, Fukumura K, Yamato A, Soda M, Yamashita Y, Choi YL, Yamasoba T, ManoH. Cancer-associated missense mutations of caspase-8 activate nuclear factor-kappaB signaling. Cancer Sci. 2013; 104:1002-1008.
27. Allen CT, Ricker JL, Chen Z, Van Waes C. Role of activated nuclear factor-kappaB in the pathogenesis and therapy of squamous cell carcinoma of the head and neck. Head Neck. 2007; 29:959-971.
28. Mitsuishi Y, Motohashi H, Yamamoto M. The Keap1-Nrf2 system in cancers: stress response and anabolic metabolism. Front Oncol. 2012; 2:200.
29. Ohkoshi A, Suzuki T, Ono M, Kobayashi T, YamamotoM. Roles of Keap1-Nrf2 system in upper aerodigestive tract carcinogenesis. Cancer Prev Res (Phila). 2013; 6: 149-159.
30. Rivera RS, Gunduz M, Nagatsuka H, Gunduz E, CengizB, Fukushima K, Beder LB, Pehlivan D, Yamanaka N, Shimizu K, Nagai N. Involvement of EphA2 in head and neck squamous cell carcinoma: mRNA expression, loss of heterozygosity and immunohistochemical studies. Oncol Rep. 2008; 19:1079-1084.
31. Findlay GM, Yan L, Procter J, Mieulet V, Lamb RF. AMAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J. 2007; 403:13-20.
32. Molinolo AA, Marsh C, El Dinali M, Gangane N, JennisonK, Hewitt S, Patel V, Seiwert TY, Gutkind JS. mTOR as a Molecular Target in HPV-Associated Oral and Cervical Squamous Carcinomas. Clin Cancer Res. 2012; 18:2558-2568.
33. Koch WM, Lango M, Sewell D, Zahurak M, SidranskyD. Head and neck cancer in nonsmokers: a distinct clinical and molecular entity. Laryngoscope. 1999; 109: 1544-1551.
34. Ferris RL, Martinez I, Sirianni N, Wang J, Lopez-Albaitero A, Gollin SM, Johnson JT, Khan S. Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN): a natural disease model provides insights into viral carcinogenesis. Eur J Cancer. 2005; 41:807-815.
35. Steenbergen RD, Hermsen MA, Walboomers JM, JoenjeH, Arwert F, Meijer CJ, Snijders PJ. Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and 18q21 in an oral carcinoma and its derivative cell line. Cancer Res. 1995; 55:5465-5471.
36. Adelstein DJ, Ridge JA, Gillison ML, Chaturvedi AK, D'Souza G, Gravitt PE, Westra W, Psyrri A, KastWM, Koutsky LA, Giuliano A, Krosnick S, Trotti A, SchullerDE, Forastiere A, Ullmann CD. Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9-10, 2008. Washington, D.C: Head Neck 2009; 31:1393-1422.
37. Gonzalez-Zulueta M, Bender CM, Yang AS, Nguyen T, Beart RW. Van Tornout JM, Jones PA. Methylation of the 5' CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res. 1995; 55:4531-4535.
38. Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989; 243: 934-937.
39. Taylor D, Koch WM, Zahurak M, Shah K, Sidransky D, Westra WH. Immunohistochemical detection of p53 protein accumulation in head and neck cancer: correlation with p53 gene alterations. Hum Pathol. 1999; 30:1221-1225.
40. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003; 113: 685-700.
41. Pring M, Prime S, Parkinson EK, Paterson I. Dysregulated TGF-beta1-induced Smad signalling occurs as a result of defects in multiple components of the TGF-beta signalling pathway in human head and neck carcinoma cell lines. Int J Oncol. 2006; 28:1279-1285.
42. Maeda T, Hobbs RM, Merghoub T, Guernah I, ZelentA. Cordon-Cardo C, Teruya-Feldstein J, Pandolfi PP. Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature. 2005; 433:278-285.
43. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, KryukovGV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, etal. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483:603-607.
44. Li H, Wawrose JS, Gooding WE, Garraway LA, Lui VW, Peyser ND, Grandis JR. Genomic analysis of head and neck squamous cell carcinoma cell lines and human tumors: a rational approach to preclinical model selection. Mol Cancer Res. 2014; 12:571-582.
45. Nichols AC, Yoo J, Palma DA, Fung K, Franklin JH, Koropatnick J, Mymryk JS, Batada NN, Barrett JW. Frequent mutations in TP53 and CDKN2A found by next-generation sequencing of head and neck cancer cell lines. Arch Otolaryngol Head Neck Surg. 2012; 138: 732-739.
46. Wang WZ, Martin D, Molinolo AA, Patel V, Iglesias-Bartolome R, Sol Degese M, Vitale-Cross L, Chen Q, Gutkind JS. mTOR Co-Targeting in Cetuximab Resistance in Head and Neck Cancers Harboring PIK3CA and RAS Mutations. J Natl Cancer Inst. 2014; 106.
47. Kim SK, Fan Y, Papadimitrakopoulou V, Clayman G, Hittelman WN, Hong WK, Lotan R, Mao L. DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma. Cancer Res. 1996; 56:2519-2521.
48. Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med. 2001; 345:1890-1900.
49. India Project Team of the International Cancer GenomeC. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 2013; 4:2873.
50. Mirghani H, Amen F, Blanchard P, Moreau F, GuigayJ, Hartl DM, Lacau St Guily J. Treatment de-escalation in HPV-positive oropharyngeal carcinoma: Ongoing trials, critical issues and perspectives. Int J Cancer. 2014.
51. The Cancer Genome Atlas. National Cancer Institute and National Human Genome Research Institute. http://cancergenome.nih.gov/
52. Bozic I, Antal T, Ohtsuki H, Carter H, Kim D, Chen S, Karchin R, Kinzler KW, Vogelstein B, Nowak MA. Accumulation of driver and passenger mutations during tumor progression. Proc Natl Acad Sci U S A. 2010; 107:18545-18550.
53. Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell. 2012; 150:12-27.
54. Huether R, Dong L, Chen X, Wu G, Parker M, WeiL, MaJ, Edmonson MN, Hedlund EK, Rusch MC, ShurtleffSA, Mulder HL, Boggs K, Vadordaria B, ChengJ, YergeauD, etal. The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat Commun. 2014; 5:3630.
55. Schuettengruber B, Martinez AM, Iovino N, Cavalli G. Trithorax group proteins: switching genes on and keeping them active. Nat Rev Mol Cell Biol. 2011; 12:799-814.
56. Gifford CA, Ziller MJ, Gu H, Trapnell C, Donaghey J, Tsankov A, Shalek AK, Kelley DR, Shishkin AA, IssnerR, Zhang X, Coyne M, Fostel JL, Holmes L, Meldrim J, Guttman M, etal. Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell. 2013; 153:1149-1163.
57. Barradas M, Anderton E, Acosta JC, Li S, Banito A, Rodriguez-Niedenfuhr M, Maertens G, Banck M, Zhou MM, Walsh MJ, Peters G, Gil J. Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes Dev. 2009; 23:1177-1182.
58. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646-674.
59. Campbell RM, Tummino PJ. Cancer epigenetics drug discovery and development: the challenge of hitting the mark. J Clin Invest. 2014; 124:64-69.
60. Javier RT. Cell polarity proteins: common targets for tumorigenic human viruses. Oncogene. 2008; 27:7031-7046.
61. Veldman T, Liu X, Yuan H, Schlegel R. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci U S A. 2003; 100:8211-8216.
62. Hromas R, Morris J, Cornetta K, Berebitsky D, DavidsonA, Sha M, Sledge G, Rauscher F, 3rd. Aberrant expression of the myeloid zinc finger gene, MZF-1, is oncogenic. Cancer Res. 1995; 55:3610-3614.
63. Kimple RJ, Smith MA, Blitzer GC, Torres AD, Martin JA, Yang RZ, Peet CR, Lorenz LD, Nickel KP, Klingelhutz AJ, Lambert PF, Harari PM. Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res. 2013; 73:4791-4800.
64. A.K. HDNGJRE-N. (2013). The Cancer Genome Atlas: Integrated analysis of genome alterations in squamous cell carcinoma of the head and neck. 2013 ASCO Annual Meeting: J Clin Oncol), pp. (suppl; abstr 6009)
65. Oganesyan OG, Saha SK, Guo B, He JQ, Shahangian A, Zarnegar B, Perry A, Cheng G. Critical role of TRAF3 in the Toll-like receptor-dependent and-independent antiviral response. Nature. 2006; 439:208-211.
66. Li S, Labrecque S, Gauzzi MC, Cuddihy AR, Wong AH, Pellegrini S, Matlashewski GJ, Koromilas AE. The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Oncogene. 1999; 18:5727-5737.
67. Jin Y, Chen D, Cabay RJ, Wang A, Crowe DL, Zhou X. Role of microRNA-138 as a potential tumor suppressor in head and neck squamous cell carcinoma. Int Rev Cell Mol Biol. 2013; 303:357-385.
68. Wong TS, Liu XB, Chung-Wai Ho A, Po-Wing Yuen A, Wai-Man Ng R, Ignace Wei W. Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling. Int J Cancer. 2008; 123:251-257.
69. Guha GM. Blockbuster dreams for Pfizer's CDK inhibitor. Nat Biotechnol. 2013; 31:187.
70. Coombes MM, Briggs KL, Bone JR, Clayman GL, El-Naggar AK, Dent SY. Resetting the histone code at CDKN2A in HNSCC by inhibition of DNA methylation. Oncogene. 2003; 22:8902-8911.
71. Zhang Y, Feng X, We R, Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. Nature. 1996; 383:168-172.
72. Leung CT, Brugge JS. Outgrowth of single oncogene-expressing cells from suppressive epithelial environments. Nature. 2012; 482:410-413.
73. Herman JG, Graff JR, Myohanen S, Nelkin BD, BaylinSB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996; 93:9821-9826.
74. Sasagawa T, Minemoto Y, Basha W, Yamazaki H, Nakamura M, Yoshimoto H, Sakaike J, Inoue M. A new PCR-based assay amplifies the E6-E7 genes of most mucosal human papillomaviruses (HPV). Virus Res. 2000; 67:127-139.
75. DePristo MA, Banks E, Poplin R, Garimella KV, MaguireJR, Hartl C, Philippakis AA, del AngelG, RivasMA, Hanna M, McKenna A, Fennell TJ, KernytskyAM, Sivachenko AY, Cibulskis K, GabrielSB, etal. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011; 43:491-498.
76. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010; 38:e164.
77. Abaan OD, Polley EC, Davis SR, Zhu YJ, Bilke S, WalkerRL, Pineda M, Gindin Y, Jiang Y, Reinhold WC, Holbeck SL, Simon RM, Doroshow JH, Pommier Y, Meltzer PS. The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology. Cancer Res. 2013; 73:4372-4382.
78. Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the functional effect of amino acid substitutions and indels. PLoS One. 2012; 7:e46688.
79. Wu TD, Nacu S. Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics. 2010; 26:873-881.
80. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010; 26:139-140.
81. Saeed AI, Sharov V, White J, Li J, Liang W, BhagabatiN, Braisted J, Klapa M, Currier T, Thiagarajan M, SturnA, Snuffin M, Rezantsev A, Popov D, RyltsovA, KostukovichE, etal. TM4: a free, open-source system for microarray data management and analysis. Biotechniques. 2003; 34:374-378.
82. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, MeirellesGV. Clark NR, Ma'ayan A. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14:128.
83. Bindea G, Mlecnik B, Hackl H, Charoentong P, TosoliniM, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, GalonJ. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25:1091-1093.