FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma.

Autor: Al Shboul S; Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, 13133, Jordan. sofian@hu.edu.jo., Boyle S; MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK., Singh A; Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XR, Scotland, UK., Saleh T; Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, 13133, Jordan., Alrjoub M; Department of Pathology and Microbiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan., Abu Al Karsaneh O; Department of Microbiology, Pathology, and Forensic Medicine, Faculty of Medicine, The Hashemite University, Zarqa, 13133, Jordan., Mryyian A; Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, 13133, Jordan., Dawoud R; Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, 13133, Jordan., Gul S; Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XR, Scotland, UK., Abu Baker S; Department of Pathology and Microbiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan., Ball K; Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XR, Scotland, UK., Hupp T; Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XR, Scotland, UK. ted.hupp@ed.ac.uk., Brennan PM; Translational Neurosurgery, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. paul.brennan@ed.ac.uk.; Translational Neurosurgery, Department of Clinical Neurosciences, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SB, Scotland, UK. paul.brennan@ed.ac.uk.
Jazyk: angličtina
Zdroj: Brain tumor pathology [Brain Tumor Pathol] 2024 Jan; Vol. 41 (1), pp. 4-17. Date of Electronic Publication: 2023 Dec 14.
DOI: 10.1007/s10014-023-00473-6
Abstrakt: Deletion of CDKN2A occurs in 50% of glioblastomas (GBM), and IFNA locus deletion in 25%. These genes reside closely on chromosome 9. We investigated whether CDKN2A and IFNA were co-deleted within the same heterogeneous tumour and their prognostic implications. We assessed CDKN2A and IFNA14 deletions in 45 glioma samples using an in-house three-colour FISH probe. We examined the correlation between p16 INK4a protein expression (via IHC) and CDKN2A deletion along with the impact of these genomic events on patient survival. FISH analyses demonstrated that grades II and III had either wildtype (wt) or amplified CDKN2A/IFNA14, whilst 44% of GBMs harboured homozygous deletions of both genes. Cores with CDKN2A homozygous deletion (n = 11) were negative for p16 INK4a . Twenty p16 INK4a positive samples lacked CDKN2A deletion with some of cells showing negative p16 INK4a . There was heterogeneity in IFNA14/CDKN2A ploidy within each GBM. Survival analyses of primary GBMs suggested a positive association between increased p16 INK4a and longer survival; this persisted when considering CDKN2A/IFNA14 status. Furthermore, wt (intact) CDKN2A/IFNA14 were found to be associated with longer survival in recurrent GBMs. Our data suggest that co-deletion of CDKN2A/IFNA14 in GBM negatively correlates with survival and CDKN2A-wt status correlated with longer survival, and with second surgery, itself a marker for improved patient outcomes.
(© 2023. The Author(s), under exclusive licence to The Japan Society of Brain Tumor Pathology.)
Databáze: MEDLINE
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