In:
Cancer Science, Wiley, Vol. 111, No. 10 ( 2020-10), p. 3902-3911
Abstract:
Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3 ‐K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma‐tailored 48‐gene next‐generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma‐tailored 48‐gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2 , TP53 , PTEN , PDGFRA , NF1 , RB1 , CDKN2A/B , CDK4 , and the TERT promoter ( TERTp ). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 IDH ‐wildtype glioblastomas. Within these IDH ‐wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp . Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp ‐wildtype glioblastomas (43%) than in TERTp ‐mutant glioblastomas (6%) ( P = .001). Hierarchical molecular classification of IDH ‐wildtype glioblastomas revealed 3 distinct groups of IDH ‐wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA , amplification of CDK4 and PDGFRA , homozygous deletion of CDKN2A/B , and absence of TERTp mutations. This cluster was significantly associated with older age ( P = .021), higher Ki‐67 score ( P = .007), poor prognosis ( P = .012), and a periventricular tumor location. We report the development of a glioma‐tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH ‐ and TERTp ‐wildtype glioblastomas with frequent PDGFRA alterations.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6