International Journal of Head and Neck Surgery

Register      Login

VOLUME 12 , ISSUE 2 ( April-June, 2021 ) > List of Articles

Original Article

Genomics Testing in Head and Neck Cancers: Is there a Benefit?

Ravi C Nayar, Richitha V Pandit, Vishal US Rao, Mithua V Ghosh, Sataksi Chatterjee

Citation Information : Nayar RC, Pandit RV, Rao VU, Ghosh MV, Chatterjee S. Genomics Testing in Head and Neck Cancers: Is there a Benefit?. Int J Head Neck Surg 2021; 12 (2):58-64.

DOI: 10.5005/jp-journals-10001-1420

License: CC BY-NC 4.0

Published Online: 01-06-2021

Copyright Statement:  Copyright © 2021; The Author(s).


Abstract

Introduction: Elucidation of the genomic basis of head and neck cancers (HNCs) may help in reducing cancer-related mortality and morbidity. This is because prognostication by predicting disease course and treatment response will help to individualize treatment protocols. Materials and methods: This prospective pilot study used a 48-gene mutation panel on tumor tissue samples obtained from 18 patients suffering from HNCs. The clinical significance of these mutations was analyzed in terms of treatment resistance, presence of distant metastasis, family history, and disease recurrence. Results: Two patients carried germline mutations, nine carried somatic mutations and seven samples had no mutation detected on the 48-gene panel. The genomic studies detected germline mutations in BRCA and AIP, and somatic mutations in TP53, phosphatase and tensin homolog (PTEN), RB1, STK11, GNA11, and HRAS. Conclusion: The study appears to validate early genomic testing of HNC cases to modify treatment protocols and offers more specific and personalized treatment options to patients. Clinical significance: The study demonstrates the potential benefit of integrating genomic data with clinical details to map out a tailored treatment plan to benefit individual patients.


PDF Share
  1. Gupta B, Johnson NW, Kumar N. Global epidemiology of head and neck cancers: a continuing challenge. Oncology 2016;91(1):13–23. DOI: 10.1159/000446117.
  2. Hedberg ML, Goh G, Chiosea SI, et al. Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma. J Clin Invest 2016;126(1):169–180. DOI: 10.1172/JCI82066.
  3. Borad MJ, Egan JB, Condjella RM, et al. Clinical implementation of Integrated genomic profiling in patients with advanced cancers. Sci Rep 2016;6(1):25. DOI: 10.1038/s41598-016-0021-4.
  4. Idowu MO, Dumur CI, Garrett CT. Molecular Oncology Testing for Solid Tumors: A Pragmatic Approach. 1st ed., Switzerland: Springer; 2015.
  5. Greaves M, Maley CC. Clonal evolution in cancer. Nature 2012;481(7381):306–313. DOI: 10.1038/nature10762.
  6. Lang J, Borchers J, Danahey D, et al. Mutational status of overexpressed p16 in head and neck cancer: evidence for germline mutation of p16/p14ARF. Int J Oncol 2002;21(2):401–408. DOI: 10.3892/ijo.21.2.401. https://www.ncbi.nlm.nih.gov/pubmed/ 12118338.
  7. Cancer genome atlas network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015;517(7536):576–582. DOI: 10.1038/nature14129.
  8. Riaz N, Morris LG, Lee W, et al. Unraveling the molecular genetics of head and neck cancer through genome-wide approaches. Genes and Diseases 2014;1(1):75–86. DOI: 10.1016/j.gendis.2014. 07.002.
  9. Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis. 7th ed., New York: W. H. Freeman; 2000.
  10. Dancey JE, Bedard PL, Onetto N, et al. The genetic basis for cancer treatment decisions. Cell 2012;148(3):409–420. DOI: 10.1016/j.cell.2012.01.014.
  11. Agrawal N, Frederick MJ, Pickering CR, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 2011;333(6046):1154–1157. DOI: 10.1126/science.1206923.
  12. Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science 2011;333(6046):1157–1160. DOI: 10.1126/science.1208130.
  13. Pickering CR, Zhang J, Yoo SY, et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 2013;3(7):770–781. DOI: 10.1158/2159-8290.CD-12-0537.
  14. Pickering CR, Zhang J, Neskey DM, et al. Squamous cell carcinoma of the oral tongue in young non-smokers is genomically similar to tumors in older smokers. Clin Cancer Res 2014;20(14):3842–3848. DOI: 10.1158/1078-0432.CCR-14-0565.
  15. Lin DC, Meng X, Hazawa M, et al. The genomic landscape of nasopharyngeal carcinoma. Nat Genet 2014;46(8):866–871. DOI: 10.1038/ng.3006.
  16. Seiwert TY, Zuo Z, Keck MK, et al. Integrative and comparative genomic analysis of HPV-positive and HPV negative head and neck squamous cell carcinomas. Clin Cancer Res 2015;21(3):632–641. DOI: 10.1158/1078-0432.CCR-13-3310.
  17. Perdomo S, Anantharaman D, Foll M, et al. Genomic analysis of head and neck cancer cases from two high incidence regions. PLoS ONE 2018;13(1):e0191701. DOI: https://doi.org/10.1371/journal.pone.0191701.
  18. Lloyd C, Grossman A. The AIP (aryl hydrocarbon receptor-interacting protein) gene and its relation to the pathogenesis of pituitary adenomas. Endocrine 2014;46(3):387–396. [Online]. Available at: 10.1007/s12020-013-0125-6.
  19. Chahal HS, Chapple JP, Frohman LA, et al. Clinical, genetic and molecular characterization of patients with familial isolated pituitary adenomas (FIPA). Trends Endocrinol Metab 2010;21(7):419–427. [Online]. Available at: 10.1016/j.tem.2010.02.007.
  20. Welcsh PL, King MC. BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum Mol Genet 2001;10(7):705–713. DOI: 10.1093/hmg/10.7.705[Online]. Available at: https://www.ncbi.nlm.nih.gov/pubmed/11257103.
  21. Sakai W, Swisher EM, Karlan BY, et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 2008;451(7182):1116–1120. [Online]. Available at: 10.1038/nature06633.
  22. De Vita Jr. VT, Lawrence TS, et al. DeVita, Hellman and Rosenberg's Cancer Principles and Practice of Oncology, vol. p2-42 10th ed., USA: Wolters Kluwer Health; 2015. pp. 416–422.
  23. Rampias T, Giagini A, Siolos S, et al. RAS/PI3K crosstalk and cetuximab resistance in head and neck squamous cell carcinoma. Clin Cancer Res 2014;20(11):2933–2946. DOI: 10.1158/1078-0432.CCR-13-2721[Online]. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24696319.
  24. Nagai MA. Genetic alterations in head and neck squamous cell carcinomas. Head and Neck Cancer Brazil J Med Biolog Res 1999;32(7):897–904. DOI: 10.1590/S0100-879X1999000700015[Online]. Available at: http://scielo.br/pdf/bjmbr/v32n7/3409c.pdf.
  25. Liu J, Xing Y, Xu L, et al. Decreased expression of pseudogene PTENP1 promotes malignant behaviours and is associated with the poor survival of patients with HNSCC. Nature: Scient Rep 2017;7(41179):[Online]. Available at: 10.1038/srep41179.
  26. Snietura M, Jaworska M, Mlynarczyk-Liszka J, et al. PTEN as a prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck. PLoS ONE 2012;7(3):e33396. DOI: 10.1371/journal.pone.0033396.
  27. Du L, Shen J, Weems A, et al. Role of phosphatidylinositol-3-kinase pathway in head and neck squamous cell carcinoma. J Oncol 2012;2012:450179. [Online]. Available at: 10.1155/2012/450179.
  28. Jenne DE, Reimann H, Nezu J, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 1998;18(1):38–43. DOI: 10.1038/ng0198-38.
  29. Giacinti C, Giordano A. RB and cell cycle progression. Oncogene 2006;25(38):5220–5227. Available at: 10.1038/sj.onc.1209615.
  30. Knudsen ES, Wang JYJ. Targeting the RB-pathway in cancer therapy. Clin Cancer Res 2010;16(4):1094. [Online]. Available at: 10.1158/1078-0432.CCR-09-0787.
  31. Cadoni G, Boccia S, Petrelli L, et al. A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism. Acta Otorhinolaryngol Ital 2012;32(1):1–11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324962/.
  32. Varley JM. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat 2003;21(3):313–320. DOI: 10.1002/humu.10185.
  33. Hisada M, Garber JE, Li FP, et al. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 1998;90(8):606–611. DOI: 10.1093/jnci/90.8.606.
  34. Vogelstein B, Sur S, Prives C. p53: the most frequently altered gene in human cancers. Nat Educat 2010;3(9):6. Available at: http://www.nature.com/scitable/topicpage/p53-themost-frequently-altered-gene-in-14192717.
  35. Sun W, Califano JA. Sequencing the head and neck cancer genome: implications for therapy. Ann N Y Acad Sci 2015;1333(1):33–42. [Online]. Available at: 10.1111/nyas.12599.
  36. Lassaletta L, Brandáriz JA, Benito A, et al. p53 expression in locally advanced pharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1999;125(12):1356–1359. DOI: 10.1001/archotol.125.12.1356[Online]. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10604414.
  37. Mroz EA, Rocco JW. Intra-tumor heterogeneity in head and neck cancer and its clinical implications. World J Otorhinolaryngol-Head and Neck Surg 2016;2(2):60–67. [Online]. Available at: http://dx.doi.org/10.1016/j.wjorl.2016.05.007.
  38. Griewank KG, van de Nes J, Schilling B, et al. Genetic and clinico-pathologic analysis of metastatic uveal melanoma. Mod Pathol 2014;27(2):175–183. [Online]. Available at: 10.1038/modpathol.2013.138.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.