A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas

被引：42

作者：

Higa, Nayuta ^{[1
]}

Akahane, Toshiaki ^{[2
,3
]}

Yokoyama, Seiya ^{[2
]}

Yonezawa, Hajime ^{[1
]}

Uchida, Hiroyuki ^{[1
]}

Takajo, Tomoko ^{[1
]}

Kirishima, Mari ^{[2
]}

Hamada, Taiji ^{[2
]}

Matsuo, Kei ^{[2
]}

Fujio, Shingo ^{[1
]}

Hanada, Tomoko ^{[1
]}

Hosoyama, Hiroshi ^{[1
]}

Yonenaga, Masanori ^{[1
]}

Sakamoto, Akihisa ^{[1
]}

Hiraki, Tsubasa ^{[2
]}

Tanimoto, Akihide ^{[2
,3
]}

Yoshimoto, Koji ^{[1
]}

机构：

[1] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Neurosurg, Kagoshima, Japan

[2] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Pathol, Kagoshima, Japan

[3] Kagoshima Univ Hosp, Ctr Human Genome & Gene Anal, Kagoshima, Japan

来源：

CANCER SCIENCE | 2020年 / 111卷 / 10期

关键词：

1p; 19q codeletion; glioblastoma; next-generation sequencing; PDGFRAalterations; TERTpromoter; COMPARATIVE GENOMIC HYBRIDIZATION; DISEASE PROGRESSION; MUTATIONS; GLIOMA; 1P/19Q; 1P;

D O I：

10.1111/cas.14597

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, includingIDH1/2andH3-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 inIDH1/2,TP53,PTEN,PDGFRA,NF1,RB1,CDKN2A/B,CDK4, and theTERTpromoter (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 gliomas, we identified 56IDH-wildtype glioblastomas. Within theseIDH-wildtype glioblastomas, 33 samples (58.9%) showed a mutation inTERTp. Notably,PDGFRAmutations and their amplification were more commonly seen inTERTp-wildtype glioblastomas (43%) than inTERTp-mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification ofIDH-wildtype glioblastomas revealed 3 distinct groups ofIDH-wildtype glioblastomas. One major cluster was characterized by mutations inPDGFRA, amplification ofCDK4andPDGFRA, homozygous deletion ofCDKN2A/B, and absence ofTERTpmutations. 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 ofIDH- andTERTp-wildtype glioblastomas with frequentPDGFRAalterations.

引用

页码：3902 / 3911

页数：10

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