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Open Access 01-12-2018 | Research article

Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature

Authors: Christian Grønhøj, David H. Jensen, Tina Agander, Katalin Kiss, Estrid Høgdall, Lena Specht, Frederik Otzen Bagger, Finn Cilius Nielsen, Christian von Buchwald

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

The genetic profile for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) remains largely unknown. The purpose of this study was to sequence tissue material from a large cohort of locoregionally-advanced HPV+ OPSCCs.

Methods

We performed targeted deep sequencing of 395 cancer-associated genes in 114 matched tumor/normal loco-regionally advanced HPV+ OPSCCs. Mutations and copy number aberrations were determined.

Results

We identified a total of 3459 mutations with an average of 10 mutations per megabase and a median of 28 variants per sample. The most frequently mutated genes were KALRN (28%), SPTBN1 (32%), KMT2A (31%), ZNRF3 (9%), BNC2 (12%), NOTCH2 (25%), FGFR2 (12%), SMAD2 (6%), and AR (13%). Our findings were dominated by COSMIC signature 5 and 12, represented in other head and neck cancers and in hepatocellular carcinomas, respectively.

Conclusions

We have identified multiple genetic aberrations in HPV+ OPSCCs, and the COSMIC signature 12 as most prevalent. The mutations harbour both therapeutic and prognostic potential.

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Title: Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature
Authors: Christian Grønhøj
David H. Jensen
Tina Agander
Katalin Kiss
Estrid Høgdall
Lena Specht
Frederik Otzen Bagger
Finn Cilius Nielsen
Christian von Buchwald
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-4567-3

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Abstract

Background

Methods

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Conclusions

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