Genomic analysis of head and neck cancer cases from two high incidence regions.

Sandra Pérdomo ,José Eduardo Levi,Florence Le Calvez-Kelm,Matthieu Foll,Reetta Holmila,Marta Vilensky,Jerry Polesel,Lorenzo Simonato,Cristina Canova,Paul Brennan,Devasena Anantharaman,Victor Wünsch-Filho,Luciana Albina Reis Rosa,Eloíza H Tajara ,James Mckay ,Παγώνα Λάγιου ,Geoffroy Durand ,Behnoush Abedi‐Ardekani ,Ivana Holcátová

doi:10.1371/journal.pone.0191701

Abstract

We investigated how somatic changes in HNSCC interact with environmental and host risk factors and whether they influence the risk of HNSCC occurrence and outcome. 180-paired samples diagnosed as HNSCC in two high incidence regions of Europe and South America underwent targeted sequencing (14 genes) and evaluation of copy number alterations (SCNAs). TP53, PIK3CA, NOTCH1, TP63 and CDKN2A were the most frequently mutated genes. Cases were characterized by a low copy number burden with recurrent focal amplification in 11q13.3 and deletion in 15q22. Cases with low SCNAs showed an improved overall survival. We found significant correlations with decreased overall survival between focal amplified regions 4p16, 10q22 and 22q11, and losses in 12p12, 15q14 and 15q22. The mutational landscape in our cases showed an association to both environmental exposures and clinical characteristics. We confirmed that somatic copy number alterations are an important predictor of HNSCC overall survival.

Highlights

Head and neck squamous cell carcinomas (HNSCC) constitute a heterogeneous group of cancers, which include cancers arising at the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx
Head and neck carcinomas show common genomic features determined by SNVs and copy number events in driver genes and cellular pathways associated to the common histology of squamous cell types
Even though we limited our sequencing study to 14 genes, our results showed that most of the mutations described in these genes are representative of the mutational profile of head and neck cancer cases

Summary

Introduction

Head and neck squamous cell carcinomas (HNSCC) constitute a heterogeneous group of cancers, which include cancers arising at the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. These cancers are the seventh most common malignancy diagnosed worldwide [1], with areas of high incidence including Mediterranean Europe and South. Genomic analysis of HNSCC in two high incidence regions

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