Stratification of HPV‐associated and HPV‐negative oropharyngeal squamous cell carcinomas based on DNA methylation epigenotypes

While the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing in these two decades, primarily due to human papillomavirus (HPV), stratification of OPSCC into molecular subgroups showing different clinicopathological features has not been fully investigated. We performed DN...

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Veröffentlicht in:International journal of cancer 2020-05, Vol.146 (9), p.2460-2474
Hauptverfasser: Nakagawa, Takuya, Matsusaka, Keisuke, Misawa, Kiyoshi, Ota, Satoshi, Fukuyo, Masaki, Rahmutulla, Bahityar, Kunii, Naoki, Sakurai, Daiju, Hanazawa, Toyoyuki, Matsubara, Hisahiro, Okamoto, Yoshitaka, Kaneda, Atsushi
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Sprache:eng
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Zusammenfassung:While the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing in these two decades, primarily due to human papillomavirus (HPV), stratification of OPSCC into molecular subgroups showing different clinicopathological features has not been fully investigated. We performed DNA methylome analysis using Infinium 450k for 170 OPSCC cases, including 89 cases in our cohort and 81 cases reported by The Cancer Genome Atlas, together with targeted exon sequencing analysis. We stratified OPSCC by hierarchical clustering analysis using methylome data. Methylation levels of classifier markers were validated quantitatively using pyrosequencing, and area under the curve (AUC) values of receiver operating characteristics (ROC) curves were calculated. OPSCC was stratified into four epigenotypes: HPV(+) high‐methylation (OP1), HPV(+) intermediate‐methylation (OP2), HPV(−) intermediate‐methylation (OP3) and HPV(−) low‐methylation (OP4). Ten methylation marker genes were generated: five to classify HPV(+) cases into OP1 and OP2, and five to classify HPV(−) cases into OP3 and OP4. AUC values of ROC curves were 0.969 and 0.952 for the two marker panels, respectively. While significantly higher TP53 mutation and CCND1 copy number gains were observed in HPV(−) than in HPV(+) groups (p 
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.32890