Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication
Advanced 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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-04-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.839302/full |
| _version_ | 1818276182004596736 |
|---|---|
| author | Aden Ka-Yin Chan Aden Ka-Yin Chan Zhi-Feng Shi Zhi-Feng Shi Kay Ka-Wai Li Kay Ka-Wai Li Wei-Wei Wang Hong Chen Nellie Yuk-Fei Chung Danny Tat-Ming Chan Wai-Sang Poon Herbert Ho-fung Loong Xian-Zhi Liu Zhen-Yu Zhang Ying Mao Ying Mao Ho-Keung Ng Ho-Keung Ng |
| author_facet | Aden Ka-Yin Chan Aden Ka-Yin Chan Zhi-Feng Shi Zhi-Feng Shi Kay Ka-Wai Li Kay Ka-Wai Li Wei-Wei Wang Hong Chen Nellie Yuk-Fei Chung Danny Tat-Ming Chan Wai-Sang Poon Herbert Ho-fung Loong Xian-Zhi Liu Zhen-Yu Zhang Ying Mao Ying Mao Ho-Keung Ng Ho-Keung Ng |
| author_sort | Aden Ka-Yin Chan |
| collection | DOAJ |
| description | Advanced 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. |
| first_indexed | 2024-12-12T22:41:34Z |
| format | Article |
| id | doaj.art-b53c1e2d27554d8a9b60b8ab409844eb |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T22:41:34Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b53c1e2d27554d8a9b60b8ab409844eb2022-12-22T00:09:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.839302839302Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for PrognosticationAden Ka-Yin Chan0Aden Ka-Yin Chan1Zhi-Feng Shi2Zhi-Feng Shi3Kay Ka-Wai Li4Kay Ka-Wai Li5Wei-Wei Wang6Hong Chen7Nellie Yuk-Fei Chung8Danny Tat-Ming Chan9Wai-Sang Poon10Herbert Ho-fung Loong11Xian-Zhi Liu12Zhen-Yu Zhang13Ying Mao14Ying Mao15Ho-Keung Ng16Ho-Keung Ng17Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaHong Kong and Shanghai Brain Consortium (HSBC), Hong Kong, Hong Kong SAR, ChinaHong Kong and Shanghai Brain Consortium (HSBC), Hong Kong, Hong Kong SAR, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaHong Kong and Shanghai Brain Consortium (HSBC), Hong Kong, Hong Kong SAR, ChinaDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pathology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaDivision of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaDivision of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaDepartment of Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHong Kong and Shanghai Brain Consortium (HSBC), Hong Kong, Hong Kong SAR, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaHong Kong and Shanghai Brain Consortium (HSBC), Hong Kong, Hong Kong SAR, ChinaAdvanced 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.839302/fullgliomasIDH1/21p19qTERTBRAFEGFR |
| spellingShingle | Aden Ka-Yin Chan Aden Ka-Yin Chan Zhi-Feng Shi Zhi-Feng Shi Kay Ka-Wai Li Kay Ka-Wai Li Wei-Wei Wang Hong Chen Nellie Yuk-Fei Chung Danny Tat-Ming Chan Wai-Sang Poon Herbert Ho-fung Loong Xian-Zhi Liu Zhen-Yu Zhang Ying Mao Ying Mao Ho-Keung Ng Ho-Keung Ng Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication Frontiers in Oncology gliomas IDH1/2 1p19q TERT BRAF EGFR |
| title | Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication |
| title_full | Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication |
| title_fullStr | Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication |
| title_full_unstemmed | Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication |
| title_short | Combinations of Single-Gene Biomarkers Can Precisely Stratify 1,028 Adult Gliomas for Prognostication |
| title_sort | combinations of single gene biomarkers can precisely stratify 1 028 adult gliomas for prognostication |
| topic | gliomas IDH1/2 1p19q TERT BRAF EGFR |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.839302/full |
| work_keys_str_mv | AT adenkayinchan combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT adenkayinchan combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT zhifengshi combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT zhifengshi combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT kaykawaili combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT kaykawaili combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT weiweiwang combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT hongchen combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT nellieyukfeichung combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT dannytatmingchan combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT waisangpoon combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT herberthofungloong combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT xianzhiliu combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT zhenyuzhang combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT yingmao combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT yingmao combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT hokeungng combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication AT hokeungng combinationsofsinglegenebiomarkerscanpreciselystratify1028adultgliomasforprognostication |