Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients.

Autor: Łysiak M; Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden., Smits A; Department of Neuroscience and Physiology, Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden.; Department of Neuroscience, Neurology, Uppsala University, University Hospital, 75185 Uppsala, Sweden., Roodakker KR; Department of Neuroscience, Neurology, Uppsala University, University Hospital, 75185 Uppsala, Sweden., Sandberg E; Department of Neuroscience, Neurology, Uppsala University, University Hospital, 75185 Uppsala, Sweden., Dimberg A; Institute of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden., Mudaisi M; Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden.; Department of Oncology in Linköping, Linköping University, 58185 Linköping, Sweden., Bratthäll C; Department of Oncology, District Hospital, 39185 Kalmar, Sweden., Strandeus M; Department of Oncology, Ryhov Hospital, 55185 Jönköping, Sweden., Milos P; Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden.; Department of Neurosurgery in Linköping, Linköping University, 58185 Linköping, Sweden., Hallbeck M; Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden.; Department of Clinical Pathology, Linköping University, 58185 Linköping, Sweden., Söderkvist P; Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden., Malmström A; Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden.; Department of Advanced Home Care, Linköping University, 58185 Linköping, Sweden.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Mar 31; Vol. 13 (7). Date of Electronic Publication: 2021 Mar 31.
DOI: 10.3390/cancers13071619
Abstrakt: Background: Biological causes of sex disparity seen in the prevalence of cancer, including glioblastoma (GBM), remain poorly understood. One of the considered aspects is the involvement of the sex chromosomes, especially loss of chromosome Y (LOY).
Methods: Tumors from 105 isocitrate dehydrogenase (IDH) wild type male GBM patients were tested with droplet digital PCR for copy number changes of ten genes on chromosome Y. Decreased gene expression, a proxy of gene loss, was then analyzed in 225 IDH wild type GBM derived from TCGA and overall survival in both cohorts was tested with Kaplan-Meier log-rank analysis and maximally selected rank statistics for cut-off determination.
Results: LOY was associated with significantly shorter overall survival (7 vs. 14.6 months, p = 0.0016), and among investigated individual genes survival correlated most prominently with loss of the sex-determining region Y gene (SRY) (10.8 vs. 14.8 months, p = 0.0031). Gene set enrichment analysis revealed that epidermal growth factor receptor, platelet-derived growth factor receptor, and MYC proto-oncogene signaling pathways are associated with low SRY expression.
Conclusion: Our data show that deletions and reduced gene expression of chromosome Y genes, especially SRY, are associated with reduced survival of male GBM patients and connected to major susceptibility pathways of gliomagenesis.
Databáze: MEDLINE
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