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Head and neck squamous cell carcinoma (molecular pathology)

Tuesday 30 September 2014


Head and neck squamous cell carcinoma (HNSCC) is characterized by significant genomic instability that could lead to clonal diversity.

Head and neck squamous cell carcinoma (HNSCC) comprise a wide spectrum of neoplasms with different tumor biologies, prognosis and response to therapies.

Current tumor classification and traditional diagnostic methods (e.g. clinical assessment, histopathology) are limited in their capacity to determine prognosis and clinical decision-making. Despite recent improvements in treatment, the outcome for patients with HNSCC remains poor.

Similar to most tumors, several patient-related factors, (e.g. genetics and environment) and disease-related factors (e.g. tumor location, TMN staging) play a significant role on survival. Thus, the problem in defining the prognosis is that the clinical course and response to treatment differ considerably among patients.

Such interindividual variability is related to the heterogeneity of the tumor, genetic and epigenetic variations, thus reflecting the interaction of multiple biological components that result in a unique phenotype.

Integrative genomics are developed to identify the molecular pathways leading to cancer at the individual level and find novel prognostic markers for HNSCC, hence tailoring a treatment accordingly.

Exome sequencing

Inj 2014, whole-exome sequencing was performed in a total of 106 primary HNSCC tumors with matched normal DNA. Mutations were confirmed in several genes, including in TP53, CDKN2A, FAT1, PTEN, HRAS, PIK3CA, and EGFR that had been previously implicated in HNSCC. Both studies also identified mutations in NOTCH1, which had never previously been associated with HNSCC

By genes

- TP53
- FAT1

Open references

- Novel insight into mutational landscape of head and neck squamous cell carcinoma.
Gaykalova DA, Mambo E, Choudhary A, Houghton J, Buddavarapu K, Sanford T, Darden W, Adai A, Hadd A, Latham G, Danilova LV, Bishop J, Li RJ, Westra WH, Hennessey P, Koch WM, Ochs MF, Califano JA, Sun W. PLoS One. 2014 Mar 25;9(3):e93102. doi : 10.1371/journal.pone.0093102 PMID: 24667986 [Free]

- Activation of the NOTCH pathway in head and neck cancer. Sun W, Gaykalova DA, Ochs MF, Mambo E, Arnaoutakis D, Liu Y, Loyo M, Agrawal N, Howard J, Li R, Ahn S, Fertig E, Sidransky D, Houghton J, Buddavarapu K, Sanford T, Choudhary A, Darden W, Adai A, Latham G, Bishop J, Sharma R, Westra WH, Hennessey P, Chung CH, Califano JA. Cancer Res. 2014 Feb 15;74(4):1091-104. doi : 10.1158/0008-5472.CAN-13-1259 PMID: 24351288

- Oral cavity and oropharyngeal squamous cell carcinoma genomics. Tan M, Myers JN, Agrawal N. Otolaryngol Clin North Am. 2013 Aug;46(4):545-66. doi : 10.1016/j.otc.2013.04.001 PMID: 23910469 [Free]

- Tumor evolution and intratumor heterogeneity of an oropharyngeal squamous cell carcinoma revealed by whole-genome sequencing. Zhang XC, Xu C, Mitchell RM, Zhang B, Zhao D, Li Y, Huang X, Fan W, Wang H, Lerma LA, Upton MP, Hay A, Méndez E, Zhao LP. Neoplasia. 2013 Dec;15(12):1371-8. PMID: 24403859 [Free]


- Translational genomics and head and neck cancer: toward precision medicine.
Razzouk S. Clin Genet. 2014 Aug 21. doi : 10.1111/cge.12487 PMID: 25143247

- Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker TP, Brown CD, Pugh TJ, Stojanov P, Cho J, Lawrence M, Getz G, Bragelmann J, DeBoer R, Weichselbaum RR, Langerman A, Portugal LD, Blair EA, Stenson KM, Lingen MW, Cohen EE, Vokes EE, White KP, Hammerman PS. Clin Cancer Res. 2014 Jul 23. PMID: 25056374