Novel genes mediating cisplatin resistance in head and neck cancer
e22135 Background: Chemo-radiotherapy with cisplatin-based regimens offers the possibility of cure to a subset of patients with surgically non-resectable squamous carcinomas of the head and neck (HNSCC), but outcome is frequently limited by acquired drug resistance. We have sought novel genes mediating cisplatin resistance in HNSCC. Methods: We derived in vitro cisplatin resistant variants of the HN5 HNSCC cell line and performed micro-array anaylsis to identify differentially expressed genes. Differences in gene expression were confirmed by qPCR and /or western blotting. Methylation-dependent transcriptional silencing of down-regulated genes was studied by bisulphate sequencing and methylation specific PCR. Selected genes were further analysed in a cohort of stage III and IV HNSCC patients treated with cisplatin-based chemo-radiotherapy. Results: We have identified a panel of genes in which changes in expression occur with acquisition of cisplatin resistance both in vitro and, some cases, in vivo. Up-regulated genes include TAOK1, BZW1 and RECQL, whereas down-regulated genes include FAM83D, PAFAH1B2, DLL1, ABPA1 and FH. Conclusions: We report the identification of a novel panel of genes which function as determinants of cisplatin sensitivity. Analysis of expression and/or epigenetic regulation of these genes may have clinical utility in prediction of patients likely to respond to highly toxic combined modality chemo-radiotherapy. No significant financial relationships to disclose.