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Article: IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations

TitleIDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations
Authors
KeywordsCDK4 amplification
CDKN2A deletion
IDH mutant astrocytomas
PDGFRA amplification
Issue Date2020
Citation
Brain Pathology, 2020, v. 30, n. 3, p. 541-553 How to Cite?
AbstractIn the 2016, WHO classification of tumors of the central nervous system, isocitrate dehydrogenase (IDH) mutation is a main classifier for lower grade astrocytomas and IDH-mutated astrocytomas is now regarded as a single group with longer survival. However, the molecular and clinical heterogeneity among IDH mutant lower grade (WHO Grades II/III) astrocytomas have only rarely been investigated. In this study, we recruited 160 IDH mutant lower grade (WHO Grades II/III) astrocytomas, and examined PDGFRA amplification, CDKN2A deletion and CDK4 amplification by FISH analysis, TERT promoter mutation by Sanger sequencing and ATRX loss and p53 expression by immunohistochemistry. We identified PDGFRA amplification, CDKN2A homozygous deletion and CDK4 amplification in 18.8%, 15.0% and 18.1% of our cohort respectively, and these alterations occurred in a mutually exclusive fashion. PDGFRA amplification was associated with shorter PFS (P = 0.0003) and OS (P < 0.0001). In tumors without PDGFRA amplification, CDKN2A homozygous deletion or CDK4 amplification was associated with a shorter OS (P = 0.035). Tumors were divided into three risk groups based on the presence of molecular alterations: high risk (PDGFRA amplification), intermediate risk (CDKN2A deletion or CDK4 amplification) and low risk (neither CDKN2A deletion and CDK4 amplification nor PDGFRA amplification). These three risk groups were significantly different in overall survival with mean survivals of 40.5, 62.9 and 71.5 months. The high-risk group also demonstrated a shorter PFS compared to intermediate- (P = 0.036) and low-risk (P < 0.0001) groups. One limitation of this study is the relatively short follow-up period, a common confounding factor for studies on low-grade tumors. Our data illustrate that IDH mutant lower grade astrocytomas is not a homogeneous group and should be molecularly stratified for risk.
Persistent Identifierhttp://hdl.handle.net/10722/325459
ISSN
2023 Impact Factor: 5.8
2023 SCImago Journal Rankings: 1.937
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, Rui Ryan-
dc.contributor.authorShi, Zhi feng-
dc.contributor.authorZhang, Zhen yu-
dc.contributor.authorChan, Aden Ka Yin-
dc.contributor.authorAibaidula, Abudumijiti-
dc.contributor.authorWang, Wei wei-
dc.contributor.authorKwan, Johnny Sheung Him-
dc.contributor.authorPoon, Wai Sang-
dc.contributor.authorChen, Hong-
dc.contributor.authorLi, Wen cai-
dc.contributor.authorChung, Nellie Yuk Fei-
dc.contributor.authorPunchhi, Gopika-
dc.contributor.authorChu, William Ching Yuen-
dc.contributor.authorChan, Ivan Sik Hei-
dc.contributor.authorLiu, Xian zhi-
dc.contributor.authorMao, Ying-
dc.contributor.authorLi, Kay Ka Wai-
dc.contributor.authorNg, Ho Keung-
dc.date.accessioned2023-02-27T07:33:29Z-
dc.date.available2023-02-27T07:33:29Z-
dc.date.issued2020-
dc.identifier.citationBrain Pathology, 2020, v. 30, n. 3, p. 541-553-
dc.identifier.issn1015-6305-
dc.identifier.urihttp://hdl.handle.net/10722/325459-
dc.description.abstractIn the 2016, WHO classification of tumors of the central nervous system, isocitrate dehydrogenase (IDH) mutation is a main classifier for lower grade astrocytomas and IDH-mutated astrocytomas is now regarded as a single group with longer survival. However, the molecular and clinical heterogeneity among IDH mutant lower grade (WHO Grades II/III) astrocytomas have only rarely been investigated. In this study, we recruited 160 IDH mutant lower grade (WHO Grades II/III) astrocytomas, and examined PDGFRA amplification, CDKN2A deletion and CDK4 amplification by FISH analysis, TERT promoter mutation by Sanger sequencing and ATRX loss and p53 expression by immunohistochemistry. We identified PDGFRA amplification, CDKN2A homozygous deletion and CDK4 amplification in 18.8%, 15.0% and 18.1% of our cohort respectively, and these alterations occurred in a mutually exclusive fashion. PDGFRA amplification was associated with shorter PFS (P = 0.0003) and OS (P < 0.0001). In tumors without PDGFRA amplification, CDKN2A homozygous deletion or CDK4 amplification was associated with a shorter OS (P = 0.035). Tumors were divided into three risk groups based on the presence of molecular alterations: high risk (PDGFRA amplification), intermediate risk (CDKN2A deletion or CDK4 amplification) and low risk (neither CDKN2A deletion and CDK4 amplification nor PDGFRA amplification). These three risk groups were significantly different in overall survival with mean survivals of 40.5, 62.9 and 71.5 months. The high-risk group also demonstrated a shorter PFS compared to intermediate- (P = 0.036) and low-risk (P < 0.0001) groups. One limitation of this study is the relatively short follow-up period, a common confounding factor for studies on low-grade tumors. Our data illustrate that IDH mutant lower grade astrocytomas is not a homogeneous group and should be molecularly stratified for risk.-
dc.languageeng-
dc.relation.ispartofBrain Pathology-
dc.subjectCDK4 amplification-
dc.subjectCDKN2A deletion-
dc.subjectIDH mutant astrocytomas-
dc.subjectPDGFRA amplification-
dc.titleIDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/bpa.12801-
dc.identifier.pmid31733156-
dc.identifier.scopuseid_2-s2.0-85076099849-
dc.identifier.volume30-
dc.identifier.issue3-
dc.identifier.spage541-
dc.identifier.epage553-
dc.identifier.eissn1750-3639-
dc.identifier.isiWOS:000500061100001-

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