A novel infram deletion in MSH6 gene in glioma: Conversation on MSH6 mutations in brain tumors

Abstract

Objective and background: Histological and molecular information and biopsy help in the diagnosis of the type and grade of tumors and increase the value of estimation of the biological behavior of tumors. In this study, we focused on a consanguineous Iranian Family with high prevalence of brain tumors in their pedigree and reviewed the literature on MSH6 mutations in brain tumors and the treatment responses focused on Gliomas.

Method: We chose a family with a high prevalence of brain tumor in their pedigree. We studied the proband's neuroimaging and brain proton magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), biopsy result, and whole-genome sequencing.

Result: The neuroimaging and brain proton MRS reported a lesion in the right frontoparietal. The MRI revealed a large enhancible heterogenous mass in the right temporo-fronto-parieto-occipital lobes with involvement of corpus callosum which was suggestive of glioma. The patient revealed a homozygous pattern for a novel 9 base-pare deletion at the 912-914 codon on exon 4 of the MSH6 gene.

Discussion: We discuss several studies on MSH6 mutations in brain tumors and we discuss treatment responses in MSH6 mutations and the studies conducted to sensitize chemotherapy and radiotherapy resistance brain tumors to face this subject efficiently.

Conclusion: Patients should be evaluated for MMR mutation before chemo and radiotherapy, and it is valuable to follow-up these mutations during the treatment too. In temozolomide (TMZ)-resitance cases, it is suggested to use complementary strategies such as using HDACis and a combination of a STAT3 Inhibitor and an mTOR inhibitor, BER inhibition mechanism, and PARP-1 inhibitor.

Keywords: MSH6; brain tumor; glioma; temozolomide; whole exome sequencing.