The mutational spectrum of squamous-cell carcinoma of the head and neck: targetable genetic events and clinical impact

Annals of Oncology

Volumn 25, Issue 10, 2014, Pages 1889-1900

  Mountzios, G ^a   Rampias, T ^b   Psyrri, A ^c,d  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS   (Greece)

^d YALE CANCER CENTER   (United States)

Author keywords

deep sequencing; genetic aberrations; SCCHN; somatic mutations

Indexed keywords

TUMOR PROTEIN;

CARCINOGENESIS; CARCINOMA, SQUAMOUS CELL; CELL DIFFERENTIATION; DNA SEQUENCE; GENETICS; HEAD AND NECK NEOPLASMS; HIGH THROUGHPUT SEQUENCING; HUMAN; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; MUTATION; PATHOLOGY;

CARCINOGENESIS; CARCINOMA, SQUAMOUS CELL; CELL DIFFERENTIATION; HEAD AND NECK NEOPLASMS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASM PROTEINS; PATHOLOGY, MOLECULAR; SEQUENCE ANALYSIS, DNA;

EID: 84907960016     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdu143     Document Type: Review

References (97)

1. Ferlay, J., Shin, H.R., Bray, F., et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:12 (2010), 2893–2917.
2. Gillison, M.L., Koch, W.M., Capone, R.B., et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:9 (2000), 709–720.
3. Argiris, A., Karamouzis, M.V., Raben, D., et al. Head and neck cancer. Lancet 371:9625 (2008), 1695–1709.
4. Gupta, S., Kong, W., Peng, Y., Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States. Int J Cancer 125:9 (2009), 2159–2165.
5. Lui, V.W., Hedberg, M.L., Li, H., et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov 3:7 (2013), 761–769.
6. Stransky, N., Egloff, A.M., Tward, A.D., et al. The mutational landscape of head and neck squamous cell carcinoma. Science 333:6046 (2011), 1157–1160.
7. Agrawal, N., Frederick, M.J., Pickering, C.R., et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333:6046 (2011), 1155–1158.
8. Pickering, C.R., Zhang, J., Yoo, S.Y., et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 3:7 (2013), 770–781.
9. Weinstein, J.N., Collisson, E.A., et al., Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45 (2013), 1113–1120.
10. Kandoth, C., McLellan, M.D., Vandin, F., et al. Mutational landscape and significance across 12 major cancer types. Nature 502 (2014), 333–339.
11. Von Hoff, D.D., Stephenson, J.J. Jr, Rosen, P., et al. Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol 28:33 (2010), 4877–4883.
12. Kim, E.S., Herbst, R.S., Wistuba, I.I., et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov 1:1 (2011), 44–53.
13. Walter, V., Yin, X., Wilkerson, M.D., et al. Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes. PLoS One, 8(2), 2013, e56823.
14. Chung, C.H., Parker, J.S., Karaca, G., et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell 5:5 (2004), 489–500.
15. Leemans, C.R., Braakhuis, B.J., Brakenhoff, R.H., et al. The molecular biology of head and neck cancer. Nat Rev Cancer 11:1 (2011), 9–22.
16. Brown, C.J., Lain, S., Verma, C.S., et al. Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer 9:12 (2009), 862–873.
17. Millon, R., Muller, D., Schultz, I., et al. Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance. Oral Oncol 37:8 (2001), 620–631.
18. Skinner, H.D., Sandulache, V.C., Ow, T.J., et al. TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res 18:1 (2012), 290–300.
19. Levine, A.J., The p53 tumor-suppressor gene. N Engl J Med 326:20 (1992), 1350–1352.
20. Dittmer, D., Pati, S., Zambetti, G., et al. Gain of function mutations in p53. Nat Genet 4:1 (1993), 42–46.
21. Forastiere, A., Koch, W., Trotti, A., et al. Head and neck cancer. N Engl J Med 345:26 (2001), 1890–1900.
22. Boyle, J.O., Hakim, J., Koch, W., et al. The incidence of p53 mutations increases with progression of head and neck cancer. Cancer Res 53:19 (1993), 4477–4480.
23. Brennan, J.A., Boyle, J.O., Koch, W.M., et al. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med 332:11 (1995), 712–717.
24. Soussi, T., Kato, S., Levy, P.P., et al. Reassessment of the TP53 mutation database in human disease by data mining with a library of TP53 missense mutations. Hum Mutat 25:1 (2005), 6–17.
25. Poeta, M.L., Manola, J., Goldwasser, M.A., et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med 357:25 (2007), 2552–2561.
26. Perrone, F., Bossi, P., Cortelazzi, B., et al. TP53 mutations and pathologic complete response to neoadjuvant cisplatin and fluorouracil chemotherapy in resected oral cavity squamous cell carcinoma. J Clin Oncol 28:5 (2010), 761–766.
27. Temam, S., Flahault, A., Périé, S., et al. p53 Gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck. J Clin Oncol 18:2 (2000), 385–394.
28. Cabelguenne, A., Blons, H., de Waziers, I., et al. p53 Alterations predict tumor response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma: a prospective series. J Clin Oncol 18:7 (2000), 1465–1473.
29. Ganly, I., Soutar, D.S., Brown, R., et al. p53 Alterations in recurrent squamous cell cancer of the head and neck refractory to radiotherapy. Br J Cancer 82:2 (2000), 392–398.
30. Alsner, J., Sørensen, S.B., Overgaard, J., TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck. Radiother Oncol 59:2 (2001), 179–185.
31. Poeta, M.L., Manola, J., Goldenberg, D., et al. The ligamp TP53 assay for detection of minimal residual disease in head and neck squamous cell carcinoma surgical margins. Clin Cancer Res 15:24 (2009), 7658–7665.
32. Ganly, I., Kirn, D., Eckhardt, G., et al. A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res 6:3 (2000), 798–806.
33. Nemunaitis, J., Khuri, F., Ganly, I., et al. Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol 19:2 (2001), 289–298.
34. Khuri, F.R., Nemunaitis, J., Ganly, I., et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 6:8 (2000), 879–885.
35. Nemunaitis, J., Clayman, G., Agarwala, S.S., et al. Biomarkers predict p53 Gene Therapy Efficacy in Recurrent Squamous Cell Carcinoma of the Head and Neck. Clin Cancer Res 15:24 (2009), 7719–7725.
36. Nemunaitis, J., Nemunaitis, J., Head and neck cancer: response to p53-based therapeutics. Head Neck 33:1 (2011), 131–134.
37. Pérez-Sayáns, M., Suárez-Peñaranda, J.M., Gayoso-Diz, P., et al. p16(INK4a)/CDKN2 expression and its relationship with oral squamous cell carcinoma is our current knowledge enough?. Cancer Lett 306:2 (2011), 134–141.
38. Reed, A.L., Califano, J., Cairns, P., et al. High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res 56:16 (1996), 3630–3633.
39. Weinberger, P.M., Yu, Z., Haffty, B.G., et al. Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer. Clin Cancer Res 10:17 (2004), 5684–5691.
40. Yu, Z., Weinberger, P.M., Haffty, B.G., et al. Cyclin d1 is a valuable prognostic marker in oropharyngeal squamous cell carcinoma. Clin Cancer Res 11:3 (2005), 1160–1166.
41. Califano, J., van der Riet, P., Westra, W., et al. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 56:11 (1996), 2488–2492.
42. Rosin, M.P., Cheng, X., Poh, C., et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res 6:2 (2000), 357–362.
43. van der Riet, P., Karp, D., Farmer, E., et al. Progression of basal cell carcinoma through loss of chromosome 9q and inactivation of a single p53 allele. Cancer Res 54:1 (1994), 25–27.
44. Brieger, J., Pongsapich, W., Mann, S.A., et al. Demethylation treatment restores hic1 expression and impairs aggressiveness of head and neck squamous cell carcinoma. Oral Oncol 46:9 (2010), 678–683.
45. Timmermann, S., Hinds, P.W., Münger, K., Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2’-deoxycytidine treatment induces a senescence-like state. Oncogene 17:26 (1998), 3445–3453.
46. Wang, L., Qi, X., Sun, Y., et al. Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity. Cancer Gene Ther 9:10 (2002), 819–824.
47. Grandis, J.R., Tweardy, D.J., Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 53:15 (1993), 3579–3584.
48. Psyrri, A., Yu, Z., Weinberger, P.M., et al. Quantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis. Clin Cancer Res 11:16 (2005), 5856–5862.
49. Bonner, J.A., Harari, P.M., Giralt, J., et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:6 (2006), 567–578.
50. Sok, J.C., Coppelli, F.M., Thomas, S.M., et al. Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res 12:17 (2006), 5065–5083.
51. Hama, T., Yuza, Y., Suda, T., et al. Functional mutation analysis of EGFR family genes and corresponding lymph node metastases in head and neck squamous cell carcinoma. Clin Exp Metastasis 29:1 (2012), 19–25.
52. Loyo, M., Li, R.J., Bettegowda, C., et al. Lessons learned from next-generation sequencing in head and neck cancer. Head Neck 35:3 (2013), 454–463.
53. Morris, L.G., Taylor, B.S., Bivona, T.G., et al. Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers. Proc Natl Acad Sci USA 108:47 (2011), 19024–19029.
54. Okami, K., Wu, L., Riggins, G., et al. Analysis of PTEN/MMAC1 alterations in aerodigestive tract tumors. Cancer Res 58:3 (1998), 509–511.
55. Shao, X., Tandon, R., Samara, G., et al. Mutational analysis of the PTEN gene in head and neck squamous cell carcinoma. Int J Cancer 77:5 (1998), 684–688.
56. Qiu, W., Schönleben, F., Li, X., et al. PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res 12:5 (2006), 1441–1446.
57. Nicolas, M., Wolfer, A., Raj, K., et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 33:3 (2003), 416–421.
58. Holsinger, F.C., Piha-Paul, S.A., Janku, F., et al. Biomarker-directed therapy of squamous carcinomas of the head and neck: targeting PI3K/PTEN/mTOR pathway. J Clin Oncol 31:9 (2013), e137–e140.
59. Janku, F., Wheler, J.J., Naing, A., et al. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res 73:1 (2013), 276–284.
60. Segrelles, C., Ruiz, S., Perez, P., et al. Functional roles of Akt signaling in mouse skin tumorigenesis. Oncogene 21:1 (2002), 53–64.
61. Grünwald V, Keilholz U, Boehm A, et al. Temsirolimus is active in refractory squamous-xell carcinoma of the head and neck (SCCHN) failing platinum-based chemotherapy and cetuximab: efficacy and toxicity data from the phase II TEMHEAD study. European Society of Oncology Annual Meeting 2012 abstract 1139.
62. Artavanis-Tsakonas, S., Rand, M.D., Lake, R.J., Notch signaling: cell fate control and signal integration in development. Science 284:5415 (1999), 770–776.
63. Rangarajan, A., Talora, C., Okuyama, R., et al. Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J 20:13 (2001), 3427–3436.
64. Nickoloff, B.J., Qin, J.Z., Chaturvedi, V., et al. Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma. Cell Death Differ 9:8 (2002), 842–855.
65. Talora, C., Sgroi, D.C., Crum, C.P., et al. Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation. Genes Dev 16:17 (2002), 2252–2263.
66. Honjo, T., The shortest path from the surface to the nucleus: RBP-J kappa/Su(H) transcription factor. Genes Cells 1:1 (1996), 1–9.
67. Klinakis, A., Lobry, C., Abdel-Wahab, O., et al. A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. Nature 473:7346 (2011), 230–233.
68. Yang, A., Kaghad, M., Wang, Y., et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2:3 (1998), 305–316.
69. Senoo, M., Pinto, F., Crum, C.P., et al. p63 Is essential for the proliferative potential of stem cells in stratified epithelia”. Cell 129:3 (2007), 523–536.
70. Koster, M.I., Kim, S., Mills, A.A., et al. p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev 18:2 (2004), 126–131.
71. Mills, A.A., Zheng, B., Wang, X.J., et al. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398:6729 (1999), 708–713.
72. Truong, A.B., Kretz, M., Ridky, T.W., et al. p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev 20:22 (2006), 3185–3197.
73. Iso, T., Kedes, L., Hamamori, Y., HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol 194:3 (2003), 237–255.
74. Nguyen, B.C., Lefort, K., Mandinova, A., et al. Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes Dev 20:8 (2006), 1028–1042.
75. Sasaki, Y., Ishida, S., Morimoto, I., et al. The p53 family member genes are involved in the Notch signal pathway. J Biol Chem 277:1 (2002), 719–724.
76. Wu, G., Nomoto, S., Hoque, M.O., DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development. Cancer Res 63:10 (2003), 2351–2357.
77. Shaw, R.J., Liloglou, T., Rogers, S.N., et al. Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing. Br J Cancer 94:4 (2006), 561–568.
78. Ogi, K., Toyota, M., Ohe-Toyoa, M., et al. Aberrant methylation of multiple genes and clinicopathological features in oral squamous cell carcinoma. Clin Cancer Res 8:10 (2002), 3164–3171.
79. Weber, M., Davies, J.J., Wittig, D., Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37:8 (2002), 853–862.
80. Takeshima, M., Saitoh, M., Kusano, K., High frequency of hypermethylation of p14, p15 and p16 in oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka. J Oral Pathol Med 37:8 (2008), 475–479.
81. Sailasree, R., Abhilash, A., Sathyan, K.M., et al. Differential roles of p16INK4A and p14ARF genes in prognosis of oral carcinoma. Cancer Epidemiol Biomarkers Prev 17:2 (2008), 414–420.
82. Yeh, K.T., Chang, J.G., Lin, T.H., Epigenetic changes of tumor suppressor genes, P15, P16, VHL and P53 in oral cancer. Oncol Rep 10:3 (2003), 659–663.
83. Shintani, S., Nakahara, Y., Mihara, M., et al. Inactivation of the p14(ARF), p15(INK4B) and p16(INK4A) genes is a frequent event in human oral squamous cell carcinomas. Oral Oncol 37:6 (2001), 498–504.
84. Nishimine, M., Nakamura, M., Kishi, M., et al. Alterations of p14ARF and p16INK4a genes in salivary gland carcinomas. Oncol Rep 10:3 (2003), 555–560.
85. Psyrri, A., Seiwert, T., Jimeno, A., Molecular Pathways in Head and Neck Cancer: EGFR, PI3K, and More. ASCO Educational Book, 2013.
86. Mills, A.A., Throwing the cancer switch: reciprocal roles of polycomb and trithorax proteins. Nat Rev Cancer 10:10 (2010), 669–682.
87. Rampias, T., Sasaki, C., Weinberger, P., et al. E6 and e7 gene silencing and transformed phenotype of human papillomavirus 16-positive oropharyngeal cancer cells”. J Natl Cancer Inst 101:6 (2009), 412–423.
88. Burtness, B., Bauman, J.E., Galloway, T., Novel targets in HPV-negative head and neck cancer: overcoming resistance to EGFR inhibition. Lancet Oncol 14:8 (2013), e302–e309.
89. Marshall, M.E., Hinz, T.K., Kono, S.A., et al. Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin Cancer Res 17:15 (2011), 5016–5025.
90. Gyanchandani, R., Ortega Alves, M.V., Myers, J.N., et al. A proangiogenic signature is revealed in FGF-mediated bevacizumab-resistant head and neck squamous cell carcinoma. Mol Cancer Res 11:12 (2013), 1585–1596.
91. Dorsey, K., Agulnik, M., Promising new molecular targeted therapies in head and neck cancer. Drugs 73:4 (2013), 315–325.
92. Jameson, M.J., Taniguchi, L.E., VanKoevering, K.K., et al. Activation of the insulin-like growth factor-1 receptor alters p27 regulation by the epidermal growth factor receptor in oral squamous carcinoma cells. J Oral Pathol Med 42:4 (2013), 332–338.
93. Thariat, J., Bensadoun, R.J., Etienne-Grimaldi, M.C., et al. Contrasted outcomes to gefitinib on tumoral IGF1R expression in head and neck cancer patients receiving postoperative chemoradiation (GORTEC trial 2004-02). Clin Cancer Res 18:18 (2012), 5123–5133.
94. Mountzios, G., Kostopoulos, I., Kotoula, V., et al. Insulin-like growth factor 1 receptor (IGF1R) expression and survival in operable squamous-cell laryngeal cancer. PLoS One, 8(1), 2013, e54048.
95. Ghandri, N., Gabbouj, S., Farhat, K., et al. Association of HLA-G polymorphisms with nasopharyngeal carcinoma risk and clinical outcome. Hum Immunol 72:2 (2011), 150–158.
96. Sunyaev, S., Ramensky, V., Koch, I., et al. Bork Prediction of deleterious human alleles. Hum Mol Genet 10:6 (2001), 591–597.
97. Ramensky, V., Bork, P., Sunyaev, S., Human non-synonymous SNPs: server and survey. Nucleic Acids Res 30:17 (2002), 3894–3900.