Comprehensive Genomic Review of TCGA Head and Neck Squamous Cell Carcinomas (HNSCC).

Mario Pérez Sayáns,Andrés Blanco Carrión,José Manuel Suárez Peñaranda,Alejandro Ismael Lorenzo Pouso,Abel García García,Cintia Micaela Chamorro Petronacci,Elena Padín Iruegas

doi:10.3390/jcm8111896

Abstract

The aim of this present study was to comprehensively describe somatic DNA alterations and transcriptional alterations in the last extension of the HNSCC subsets in TCGA, encompassing a total of 528 tumours. In order to achieve this goal, transcriptional analysis, functional enrichment assays, survival analysis, somatic copy number alteration analysis and somatic alteration analysis were carried out. A total of 3491 deregulated genes were found in HNSCC patients, and the functional analysis carried out determined that tissue development and cell differentiation were the most relevant signalling pathways in upregulated and downregulated genes, respectively. Somatic copy number alteration analysis showed a “top five” altered HNSCC genes: CDKN2A (deleted in 32.03% of patients), CDKN2B (deleted in 28.34% of patients), PPFIA1 (amplified in 26.02% of patients), FADD (amplified in 25.63% of patients) and ANO1 (amplified in 25.44% of patients). Somatic mutations analysis revealed TP53 mutation in 72% of the tumour samples followed by TTN (39%), FAT1 (23%) and MUC16 (19%). Another interesting result is the mutual exclusivity pattern that was discovered between the TP53 and PIK3CA mutations, and the co-occurrence of CDKN2A with the TP53 and FAT1 alterations. On analysis to relate differential expression genes and somatic copy number alterations, some genes were overexpressed and amplified, for example, FOXL2, but other deleted genes also showed overexpression, such as CDKN2A. Survival analysis revealed that overexpression of some oncogenes, such as EGFR, CDK6 or CDK4 were associated with poorer prognosis tumours. These new findings help us to develop new therapies and programs for the prevention of HNSCC.

Highlights

Head and neck squamous cell carcinomas (HNSCCs) encompass a heterogeneous group of malignancies that begin in the upper aerodigestive tract mucosae
We identified 3491 differentially expressed genes (DEGs) in HNSCC tumour samples when compared to healthy oral tissue
After analysing missense mutations and truncated mutations in oncogenes and tumour suppressors, we have found that generally, in oncogenes, missense mutations are superior to truncated mutations but not in tumour suppressors, except from those more famous in HNSCC as CDKN2, FAT1 or PTEN

Summary

Introduction

Head and neck squamous cell carcinomas (HNSCCs) encompass a heterogeneous group of malignancies that begin in the upper aerodigestive tract mucosae. According to the GLOBOCAN project, HNSCCs are the sixth most common cancers worldwide, with an annual estimation of 355,000 attributable deaths and 633,000 incident cases [3]. In this vein, the overall five-year survival rate for HNSCCs has not decreased in recent decades and it is still about 60% [4]. Tobacco use and alcohol intake are the best-characterised modifiable risk factors of HNSCCs, its magnitude factors may change significantly within the variation of each subgroup [6]

Objectives

Methods

Results

Discussion

Conclusion