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Targeted genome sequencing of negative and positive human papillomavirus induced conjunctival carcinomas
Author(s) -
Ramberg Ingvild,
Toft Peter,
Jensen David,
Buchwald Christian,
Cilius Nielsen Finn,
Funding Mikkel,
Heegaard Steffen
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.5336
Subject(s) - missense mutation , biology , gene , cancer research , mutation , pathology , medicine , genetics
Purpose To perform a comprehensive targeted genome sequencing of premalignant and malignant conjunctival squamous cell carcinomas in order to elucidate the genetic background of these tumours. Methods Due to the scant knowledge of the mutational landscape in conjunctival carcinomas, we performed next‐generation sequencing of 509 genes commonly affected in human cancers. We sequenced a total of 110 tumours; 31 invasive carcinomas, 55 preinvasive and 24 coupled recurrent tumours. All cases were investigated for presence of human papillomavirus (HPV) by p16 immunohistochemistry, messenger RNA in situ hybridisation and HPV DNA PCR, and HPV positive tumours were genotyped by sequencing. Results 21.4 % of the tumours were HPV positive. High‐risk HPV16 was the most commonly detected genotype (70%). There was an average of 9 mutations identified in each tumour. C to T substitutions at pyrimidine sites leading to missense mutations were the most common type of mutations. HPV negative tumours frequently harboured mutations in FGFR2, IGF1R, and EP400, whereas HPV positive tumours most frequently harboured mutations in the FOS, AKT2 and mTOR genes. Conclusions Ultraviolet radiation (UV)‐induced signature mutations were found in both HPV positive and HPV negative tumours. Different genes were affected in tumours harbouring high‐risk HPV positive tumours compared to HPV negative tumours.