PO-085 Mutational profiling can identify laryngeal dysplasia at risk of progression to invasive carcinoma

• Published in: ESMO open 2018-07, Vol.3 (Suppl 2), p.A259-A259
• Main Authors: Manterola, L, Aguirre, P, Gaafar, A, Elorriaga, K, Sistiaga, JA, Zabala, A, Ispizua, A, Garcia-Pedrero, JM, Rodrigo, JP, Lawrie, C
• Format: Article
• Language: English
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2018-EACR25.613

IntroductionEarly diagnosis of laryngeal squamous cell carcinoma (LSCC) at the stage of laryngeal dysplasia could greatly improve the outcome of affected patients. However, there is a lack of reliable biomarkers to identify patients at risk of progression. It is generally accepted that progression to invasive carcinoma is associated with cumulative genetic alterations. We therefore compared fort the first time the mutational profile of both progressing dysplasia (PD) and non-progressing dysplasia(NPD) cases.Material and methodsWe carried out targeted next-generation sequencing (NGS) on 6 NPD and 5 PD cases along with patient-matched LSCC and non tumour tissue (19 samples in total). These data were validated by Sanger sequencing and TaqMan-based qPCR assays, and extended to a validation cohort of 36 NPD and 19 paired PD/LSCC cases. We further extended the analysis in silico to 530 HNSCC cases by interrogating the TCGA database.Results and discussionsMutations in PIK3CA and FGFR3 were detected in PD and LSCC cases, as well as other HNSCC cases, but absent in NPD cases. In contrast, mutations in JAK3, MET and FBXW7 were found in NPD cases but not PD, LSCC or other HNSCC cases. TP53 was the most frequently mutated gene in both PD and NPD cases. With the exception of R248W, mutations were mutually exclusive. Moreover, five of seven PD mutations were located in motif H2 of p53, whereas none of the NPD mutations were.ConclusionThe mutational profile of laryngeal dysplasia has utility for the early detection of patients at risk of progression.