Publications
Genomic analysis of HPV-positive versus HPV-negative oesophageal adenocarcinoma identifies a differential mutational landscape
Abstract
BACKGROUND: High-risk human papillomavirus (hr-HPV) has been implicated in a subset of patients with oesophageal adenocarcinoma (OAC). We therefore hypothesised that HPV associated OAC may have distinct genomic aberrations compared with viral negative oesophageal cancer. METHODS: Whole exome sequencing was performed to explore the mutational landscape and potential molecular signature of HPV-positive versus HPV-negative OAC. Four hr-HPV-positive and 8 HPV-negative treatment-naive fresh-frozen OAC tissue specimens and matched normal tissue were analysed to identify somatic genomic mutations. Data were subjected to cancer driver gene identification and pathway analysis. RESULTS: The HPV-positive cohort harboured approximately 50% less non-silent somatic mutations than the virus-negative patients with oesophageal cancer (1.31 mutations/Mb vs 2.56 mutations/Mb, p=0.048). TP53 aberrations were absent in the HPV-positive OAC group whereas 50% of the HPV-negative patients with OAC exhibited TP53 mutations. HPV-negative cancers were enriched with non-silent mutations in cancer driver genes, but not HPV-positive tumours. Enriched A>C transversions at adenine-adenine (AA) dinucleotide was observed in 5/7 Siewert class I OAC samples but none (0/5) in Siewert class II tumours (p=0.027). CONCLUSIONS: These findings demonstrate distinct genomic differences between HPV-positive and HPV-negative OACs indicating different biological mechanisms of tumour formation.
Type | Journal |
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ISBN | 1468-6244 (Electronic) 0022-2593 (Linking) |
Authors | Rajendra, S. ; Wang, B. ; Merrett, N. ; Sharma, P. ; Humphris, J. ; Lee, H. C. ; Wu, J.; |
Responsible Garvan Author | (missing name) |
Publisher Name | JOURNAL OF MEDICAL GENETICS |
Published Date | 2016-04-01 |
Published Volume | 53 |
Published Pages | 227-31 |
Status | Published in-print |
URL link to publisher's version | http://www.ncbi.nlm.nih.gov/pubmed/26470716 |
OpenAccess link to author's accepted manuscript version | https://publications.gimr.garvan.org.au/open-access/13290 |