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.

Centro di Riferimento Oncologico Aviano National Cancer Institute Aviano Italy

Charles University of Prague Prague Czech Republic

Faculdade de Saúde Pública Universidade de São Paulo São Paulo Brazil

Institute of Nutrition Genetics and Metabolism Research Faculty of Medicine Universidad El Bosque Bogotá Colombia

Instituto Angel Roffo Buenos Aires Argentina

Instituto de Medicina Tropical de SP Universidade de São Paulo USP São Paulo Brazil

International Agency for Research on Cancer Lyon France

Laboratory of Public Health and Population Studies Padova Italy

School of Medicine of São José do Rio Preto São José do Rio Preto Brazil

University of Athens Medical School Athens Greece

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