Analysis of the mutational landscape of pancreatic neuroendocrine tumours before and after temozolomide treatment

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Introduction: Temozolomide (TMZ) is an alkylating agent and standard treatment for pancreatic neuroendocrine tumours (pNET). Resistance to TMZ may be acquired through inactivation of the mismatch repair system, leading to high tumour mutation burden (hTMB).

Aim(s): To assess the emergence of hTMB upon TMZ treatment in a retrospective cohort of pNET.

Materials and methods: We performed comprehensive genomic sequencing (CGS) of 174 cancer genes on pNET with complete clinical data and available histological samples before and after TMZ. Clonality of nonsynonymous mutations was obtained calculating the cancer cell fraction to distinguish clonal/subclonal events. The threshold for hTMB was set to 10 mut/Mb.

Conference:

Presenting Author: Trevisani E

Authors: Trevisani E, Borghesani M, Reni A, Agnoletto C, Luchini C,

Keywords: neuroendocrine, next generation sequencing, temozolomide, hypermutation, tumour mutational burden,