Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients

Cancers

TimA. Iseli¹  David Wiesenfeld¹  MichaelJ. McCullough²  OliverM. Sieber³  Dmitri Mouradov³  Kendrick Koo³  AntonyW. Burgess³  ChristopherM. Angel⁴ 

[1] Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia;Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia;Personalised Oncology Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC 3052, Australia;Peter MacCallum Cancer Centre, Parkville, VIC 3000, Australia;

关键词: oral cancer;    tobacco;    alcohol;    human papilloma virus;    targeted sequencing;    DNA copy number;   

DOI  :  10.3390/cancers13051029

来源: DOAJ

【 摘 要 】

Molecular alterations in 176 patients with oral squamous cell carcinomas (OSCC) were evaluated to delineate differences in non-smoking non-drinking (NSND) patients. Somatic mutations and DNA copy number variations (CNVs) in a 68-gene panel and human papilloma virus (HPV) status were interrogated using targeted next-generation sequencing. In the entire cohort, TP53 (60%) and CDKN2A (24%) were most frequently mutated, and the most common CNVs were EGFR amplifications (9%) and deletions of BRCA2 (5%) and CDKN2A (4%). Significant associations were found for TP53 mutation and nodal disease, lymphovascular invasion and extracapsular spread, CDKN2A mutation or deletion with advanced tumour stage, and EGFR amplification with perineural invasion and extracapsular spread. PIK3CA mutation, CDKN2A deletion, and EGFR amplification were associated with worse survival in univariate analyses (p < 0.05 for all comparisons). There were 59 NSND patients who tended to be female and older than patients who smoke and/or drink, and showed enrichment of CDKN2A mutations, EGFR amplifications, and BRCA2 deletions (p < 0.05 for all comparisons), with a younger subset showing higher mutation burden. HPV was detected in three OSCC patients and not associated with smoking and drinking habits. NSND OSCC exhibits distinct genomic profiles and further exploration to elucidate the molecular aetiology in these patients is warranted.

【 授权许可】

Unknown