Lack of KBTBD4 Mutations in Molecularly Classified Brazilian Medulloblastomas

Abstract

Medulloblastoma is the most frequent malignant brain tumor in children, representing 20% of all childhood brain tumors. Currently, medulloblastomas are molecularly classified in 4 subgroups that are associated with distinctive clinicopathological features. KBTBD4 mutations were recently described in a subset of MBGRP3 and MBGRP4 medulloblastomas subgroups. However, no other studies reported KBTBD4 mutations in medulloblastomas. Thus, our aim was to investigate KBTBD4 mutations in a Brazilian series of medulloblastoma. We evaluated 128 medulloblastoma patients molecularly classified from 4 Brazilian reference centers. DNA from formalin-fixed, paraffin-embedded samples was screened for KBTBD4 hotspot mutations by Sanger sequencing. Most of the patients were male, average age was 16.5 years old and average overall survival was 55.9 months. The predominant histological subtype was the classic subtype, followed by nodular/desmoplastic, and the predominant medulloblastoma molecular subtype was the MBSHH subgroup (46%), followed by MBGRP3 and MBGRP4 (19%/each), and MBWNT (16%). Among the 128 samples, 111 were successfully sequenced. No KBTBD4 mutations were identified in 111 samples. Our findings suggest that KBTBD4 mutations are uncommon in Brazilian MBGRP3 and MBGRP4 medulloblastomas subgroups. Further studies in a larger series of MBGRP3 and MBGRP4 medulloblastomas are warranted to better assess role of KBTBD4 mutations.

Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup

“…The 22-gene panel has been already reported for a set of these patients in two previous studies. 7,18 In addition, to improve the prognostication of medulloblastoma, nine medulloblastoma-related genes (GNAS, TP53, PTEN, MYCN, TERT, SOX2, MET, GFI1, and GFI1B) were included in the 22-gene panel.…”

Research progress in molecular pathology markers in medulloblastoma

“…KBTBD4 gene insertions are located at a hotspot region (codons 308-313) and have been reported exclusively in non-WNT/non-SHH MBs [25,48,49]. However, researchers from Brazil analyzed a series of 111 MBs, including 48 cases from the non-WNT/non-SHH subtype; none of the 48 harbored any KBTBD4 mutations at the hotspot region [74]. This may have been the result of population differences or small sample size.…”