Temozolomide treatment induces an MMR-dependent hypermutator phenotype in well-differentiated pancreatic neuroendocrine tumors

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Introduction: Temozolomide (TMZ), an alkylating agent, is an effective treatment used in multiple tumor types including advanced pancreatic neuroendocrine tumors (PanNET). In glioblastomas, TMZ induces a hypermutator and hyperprogressor phenotype in a subset of patients through MMR deficiency. In advanced colon cancer, TMZ priming increases tumor mutational burden (TMB), favouring immunotherapy efficacy.

Aim(s): The aim of this study was to assess the molecular impact of TMZ on PanNET.

Materials and methods: 57 patients with low grade G1/G2 PanNET and without early progression to TMZ, treated in one expert center were selected. Sequencing of 500 cancer genes was performed on 23 matched pre/post-TMZ samples, without intercurrent DNA-damaging treatment. Results were validated in an independent cohort of 1079 PanNETs profiled by Foundation Medicine.

Conference:

Presenting Author: de Mestier L

Authors: de Mestier L, Cohen D, de Rycke O, Masliah Planchon J, Fleischmann Z,

Keywords: temozolomide, hypermutation, pancreatic neuroendocrine tumor,