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Article: Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication

TitleCombinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication
Authors
Keywords10q
1p19q
BRAF
EGFR
gliomas
H3
IDH1/2
TERT
Issue Date2022
Citation
Frontiers in Oncology, 2022, v. 12, article no. 839302 How to Cite?
AbstractAdvanced genomic techniques have now been incorporated into diagnostic practice in neuro-oncology in the literature. However, these assays are expensive and time-consuming and demand bioinformatics expertise for data interpretation. In contrast, single-gene tests can be run much more cheaply, with a short turnaround time, and are available in general pathology laboratories. The objective of this study was to establish a molecular grading scheme for adult gliomas using combinations of commonly available single-gene tests. We retrospectively evaluated molecular diagnostic data of 1,275 cases of adult diffuse gliomas from three institutions where we were testing for IDH1/2 mutation, TERTp mutation, 1p19q codeletion, EGFR amplification, 10q deletion, BRAF V600E, and H3 mutations liberally in our regular diagnostic workup. We found that a molecular grading scheme of Group 1 (1p19q codeleted, IDH mutant), Group 2 (IDH mutant, 1p19q non-deleted, TERT mutant), Group 3 (IDH mutant, 1p19q non-deleted, TERT wild type), Group 4 (IDH wild type, BRAF mutant), Group 5 (IDH wild type, BRAF wild type and not possessing the criteria of Group 6), and Group 6 (IDH wild type, and any one of TERT mutant, EGFR amplification, 10q deletion, or H3 mutant) could significantly stratify this large cohort of gliomas for risk. A total of 1,028 (80.6%) cases were thus classifiable with sufficient molecular data. There were 270 cases of molecular Group 1, 59 cases of molecular Group 2, 248 cases of molecular Group 3, 27 cases of molecular Group 4, 117 cases of molecular Group 5, and 307 cases of molecular Group 6. The molecular groups were independent prognosticators by multivariate analyses and in specific instances, superseded conventional histological grades. We were also able to validate the usefulness of the Groups with a cohort retrieved from The Cancer Genome Atlas (TCGA) where similar molecular tests were liberally available. We conclude that a single-gene molecular stratification system, useful for fine prognostication, is feasible and can be adopted by a general pathology laboratory.
Persistent Identifierhttp://hdl.handle.net/10722/325563
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, Aden Ka Yin-
dc.contributor.authorShi, Zhi Feng-
dc.contributor.authorLi, Kay Ka Wai-
dc.contributor.authorWang, Wei Wei-
dc.contributor.authorChen, Hong-
dc.contributor.authorChung, Nellie Yuk Fei-
dc.contributor.authorChan, Danny Tat Ming-
dc.contributor.authorPoon, Wai Sang-
dc.contributor.authorLoong, Herbert Ho fung-
dc.contributor.authorLiu, Xian Zhi-
dc.contributor.authorZhang, Zhen Yu-
dc.contributor.authorMao, Ying-
dc.contributor.authorNg, Ho Keung-
dc.date.accessioned2023-02-27T07:34:19Z-
dc.date.available2023-02-27T07:34:19Z-
dc.date.issued2022-
dc.identifier.citationFrontiers in Oncology, 2022, v. 12, article no. 839302-
dc.identifier.urihttp://hdl.handle.net/10722/325563-
dc.description.abstractAdvanced genomic techniques have now been incorporated into diagnostic practice in neuro-oncology in the literature. However, these assays are expensive and time-consuming and demand bioinformatics expertise for data interpretation. In contrast, single-gene tests can be run much more cheaply, with a short turnaround time, and are available in general pathology laboratories. The objective of this study was to establish a molecular grading scheme for adult gliomas using combinations of commonly available single-gene tests. We retrospectively evaluated molecular diagnostic data of 1,275 cases of adult diffuse gliomas from three institutions where we were testing for IDH1/2 mutation, TERTp mutation, 1p19q codeletion, EGFR amplification, 10q deletion, BRAF V600E, and H3 mutations liberally in our regular diagnostic workup. We found that a molecular grading scheme of Group 1 (1p19q codeleted, IDH mutant), Group 2 (IDH mutant, 1p19q non-deleted, TERT mutant), Group 3 (IDH mutant, 1p19q non-deleted, TERT wild type), Group 4 (IDH wild type, BRAF mutant), Group 5 (IDH wild type, BRAF wild type and not possessing the criteria of Group 6), and Group 6 (IDH wild type, and any one of TERT mutant, EGFR amplification, 10q deletion, or H3 mutant) could significantly stratify this large cohort of gliomas for risk. A total of 1,028 (80.6%) cases were thus classifiable with sufficient molecular data. There were 270 cases of molecular Group 1, 59 cases of molecular Group 2, 248 cases of molecular Group 3, 27 cases of molecular Group 4, 117 cases of molecular Group 5, and 307 cases of molecular Group 6. The molecular groups were independent prognosticators by multivariate analyses and in specific instances, superseded conventional histological grades. We were also able to validate the usefulness of the Groups with a cohort retrieved from The Cancer Genome Atlas (TCGA) where similar molecular tests were liberally available. We conclude that a single-gene molecular stratification system, useful for fine prognostication, is feasible and can be adopted by a general pathology laboratory.-
dc.languageeng-
dc.relation.ispartofFrontiers in Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject10q-
dc.subject1p19q-
dc.subjectBRAF-
dc.subjectEGFR-
dc.subjectgliomas-
dc.subjectH3-
dc.subjectIDH1/2-
dc.subjectTERT-
dc.titleCombinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fonc.2022.839302-
dc.identifier.pmid35558510-
dc.identifier.pmcidPMC9090434-
dc.identifier.scopuseid_2-s2.0-85131749802-
dc.identifier.volume12-
dc.identifier.spagearticle no. 839302-
dc.identifier.epagearticle no. 839302-
dc.identifier.eissn2234-943X-
dc.identifier.isiWOS:000805958700001-

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