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We sought to analyse the androgen receptor (AR) in glioblastoma (GBM) due to the location of the AR gene on chromosome X, often reported with shorter survival and higher prevalence of GBM among males. Copy number (CN) and mRNA expression of AR were tested with droplet digital PCR in 91 fresh-frozen GBM samples and 170 formalin-fixed, paraffin-embedded samples collected at Linkoping University Hospital. The fresh-frozen cohort was also subjected to pyrosequencing methylation analysis of 17 CpG sites in the AR promoter. Additionally, the gene expression of AR was analysed in the fresh-frozen cohort and The Cancer Genome Atlas (TCGA) cohort of isocitrate dehydrogenase wild-type primary GBM (135 females and 219 males). The association of AR expression and overall survival (OS) was tested with Kaplan-Meier log rank analysis after dichotomisation by maximally selected rank statistics. We found that AR CN alterations were more common in female GBM. AR gene expression correlated with methylation levels of different CpG sites in males and females but there was no difference in expression between sexes. Survival analysis of TCGA cohort revealed the opposite effect of AR overexpression on OS of males and females, with high AR expression correlating with shorter OS in females and longer OS in males. Additional gene set enrichment analysis showed that AR expression correlated with DNA repair response, especially in the male group. In summary, we found that high AR gene expression in GBM exhibits sex-dependent effects on patient survival, which, for males, is linked to DNA repair response., Funding Agencies|Cancerfonden; LiU Cancer at Linkoping University; ALF Grants; Region Ostergotland; Medical Research Council of Southeast Sweden (FORSS)

We sought to analyse the androgen receptor (AR) in glioblastoma (GBM) due to the location of the AR gene on chromosome X, often reported with shorter survival and higher prevalence of GBM among males. Copy number (CN) and mRNA expression of AR were tested with droplet digital PCR in 91 fresh-frozen GBM samples and 170 formalin-fixed, paraffin-embedded samples collected at Linkoping University Hospital. The fresh-frozen cohort was also subjected to pyrosequencing methylation analysis of 17 CpG sites in the AR promoter. Additionally, the gene expression of AR was analysed in the fresh-frozen cohort and The Cancer Genome Atlas (TCGA) cohort of isocitrate dehydrogenase wild-type primary GBM (135 females and 219 males). The association of AR expression and overall survival (OS) was tested with Kaplan-Meier log rank analysis after dichotomisation by maximally selected rank statistics. We found that AR CN alterations were more common in female GBM. AR gene expression correlated with methylation levels of different CpG sites in males and females but there was no difference in expression between sexes. Survival analysis of TCGA cohort revealed the opposite effect of AR overexpression on OS of males and females, with high AR expression correlating with shorter OS in females and longer OS in males. Additional gene set enrichment analysis showed that AR expression correlated with DNA repair response, especially in the male group. In summary, we found that high AR gene expression in GBM exhibits sex-dependent effects on patient survival, which, for males, is linked to DNA repair response., Funding Agencies|Cancerfonden; LiU Cancer at Linkoping University; ALF Grants; Region Ostergotland; Medical Research Council of Southeast Sweden (FORSS)

We sought to analyse the androgen receptor (AR) in glioblastoma (GBM) due to the location of the AR gene on chromosome X, often reported with shorter survival and higher prevalence of GBM among males. Copy number (CN) and mRNA expression of AR were tested with droplet digital PCR in 91 fresh-frozen GBM samples and 170 formalin-fixed, paraffin-embedded samples collected at Linkoping University Hospital. The fresh-frozen cohort was also subjected to pyrosequencing methylation analysis of 17 CpG sites in the AR promoter. Additionally, the gene expression of AR was analysed in the fresh-frozen cohort and The Cancer Genome Atlas (TCGA) cohort of isocitrate dehydrogenase wild-type primary GBM (135 females and 219 males). The association of AR expression and overall survival (OS) was tested with Kaplan-Meier log rank analysis after dichotomisation by maximally selected rank statistics. We found that AR CN alterations were more common in female GBM. AR gene expression correlated with methylation levels of different CpG sites in males and females but there was no difference in expression between sexes. Survival analysis of TCGA cohort revealed the opposite effect of AR overexpression on OS of males and females, with high AR expression correlating with shorter OS in females and longer OS in males. Additional gene set enrichment analysis showed that AR expression correlated with DNA repair response, especially in the male group. In summary, we found that high AR gene expression in GBM exhibits sex-dependent effects on patient survival, which, for males, is linked to DNA repair response., Funding Agencies|Cancerfonden; LiU Cancer at Linkoping University; ALF Grants; Region Ostergotland; Medical Research Council of Southeast Sweden (FORSS)

We sought to analyse the androgen receptor (AR) in glioblastoma (GBM) due to the location of the AR gene on chromosome X, often reported with shorter survival and higher prevalence of GBM among males. Copy number (CN) and mRNA expression of AR were tested with droplet digital PCR in 91 fresh-frozen GBM samples and 170 formalin-fixed, paraffin-embedded samples collected at Linkoping University Hospital. The fresh-frozen cohort was also subjected to pyrosequencing methylation analysis of 17 CpG sites in the AR promoter. Additionally, the gene expression of AR was analysed in the fresh-frozen cohort and The Cancer Genome Atlas (TCGA) cohort of isocitrate dehydrogenase wild-type primary GBM (135 females and 219 males). The association of AR expression and overall survival (OS) was tested with Kaplan-Meier log rank analysis after dichotomisation by maximally selected rank statistics. We found that AR CN alterations were more common in female GBM. AR gene expression correlated with methylation levels of different CpG sites in males and females but there was no difference in expression between sexes. Survival analysis of TCGA cohort revealed the opposite effect of AR overexpression on OS of males and females, with high AR expression correlating with shorter OS in females and longer OS in males. Additional gene set enrichment analysis showed that AR expression correlated with DNA repair response, especially in the male group. In summary, we found that high AR gene expression in GBM exhibits sex-dependent effects on patient survival, which, for males, is linked to DNA repair response., Funding Agencies|Cancerfonden; LiU Cancer at Linkoping University; ALF Grants; Region Ostergotland; Medical Research Council of Southeast Sweden (FORSS)

We sought to analyse the androgen receptor (AR) in glioblastoma (GBM) due to the location of the AR gene on chromosome X, often reported with shorter survival and higher prevalence of GBM among males. Copy number (CN) and mRNA expression of AR were tested with droplet digital PCR in 91 fresh-frozen GBM samples and 170 formalin-fixed, paraffin-embedded samples collected at Linkoping University Hospital. The fresh-frozen cohort was also subjected to pyrosequencing methylation analysis of 17 CpG sites in the AR promoter. Additionally, the gene expression of AR was analysed in the fresh-frozen cohort and The Cancer Genome Atlas (TCGA) cohort of isocitrate dehydrogenase wild-type primary GBM (135 females and 219 males). The association of AR expression and overall survival (OS) was tested with Kaplan-Meier log rank analysis after dichotomisation by maximally selected rank statistics. We found that AR CN alterations were more common in female GBM. AR gene expression correlated with methylation levels of different CpG sites in males and females but there was no difference in expression between sexes. Survival analysis of TCGA cohort revealed the opposite effect of AR overexpression on OS of males and females, with high AR expression correlating with shorter OS in females and longer OS in males. Additional gene set enrichment analysis showed that AR expression correlated with DNA repair response, especially in the male group. In summary, we found that high AR gene expression in GBM exhibits sex-dependent effects on patient survival, which, for males, is linked to DNA repair response., Funding Agencies|Cancerfonden; LiU Cancer at Linkoping University; ALF Grants; Region Ostergotland; Medical Research Council of Southeast Sweden (FORSS)

Purpose Glioma patients have poor prognosis. The amount of detail of disease-related information patients wish to receive is not known. The aim of this study was to explore glioma patients experiences and preferences regarding receiving information on diagnosis and prognosis. Methods Semi-structured interviews were performed with patients diagnosed with glioma. The interviews were analysed by qualitative content analysis without predefined categories by two independent coders. Results Ten women and 15 men, with newly diagnosed grade II-IV glioma, age 25-76 years, were interviewed. Participants experience on diagnosis communication was either indirect, meaning they found out their diagnosis unintentionally, e.g., from their electronic health record (EHR) instead of from their doctor, this causing anxiety and feelings of abandonment, insufficiently tailored: lacking in many aspects or individualised and compassionate. Participants generally wanted to know "the truth" about diagnosis and prognosis, but what they meant varied; some desired full honest information to allow for autonomous choices, others preferred general information without details, and some wanted no bad news at all, only positive information. Participants disclosed vulnerability after receiving their diagnosis, being cast into the unknown. They expressed a need for better everyday practical information to help create some control. Supportive staff could reduce participants distress. Conclusion There is a need to further develop and implement individually tailored information to glioma patients, both in consultations and patient-accessed EHR systems, which should have safe guards for sensitive information. Not all patients want to know it all, one size does not fit all., Funding Agencies|Linkoping University; County Council of Ostergotland (ALF); Medical Research Council of Southeast Sweden Research grant; NSC Research grant

Purpose Glioma patients have poor prognosis. The amount of detail of disease-related information patients wish to receive is not known. The aim of this study was to explore glioma patients experiences and preferences regarding receiving information on diagnosis and prognosis. Methods Semi-structured interviews were performed with patients diagnosed with glioma. The interviews were analysed by qualitative content analysis without predefined categories by two independent coders. Results Ten women and 15 men, with newly diagnosed grade II-IV glioma, age 25-76 years, were interviewed. Participants experience on diagnosis communication was either indirect, meaning they found out their diagnosis unintentionally, e.g., from their electronic health record (EHR) instead of from their doctor, this causing anxiety and feelings of abandonment, insufficiently tailored: lacking in many aspects or individualised and compassionate. Participants generally wanted to know "the truth" about diagnosis and prognosis, but what they meant varied; some desired full honest information to allow for autonomous choices, others preferred general information without details, and some wanted no bad news at all, only positive information. Participants disclosed vulnerability after receiving their diagnosis, being cast into the unknown. They expressed a need for better everyday practical information to help create some control. Supportive staff could reduce participants distress. Conclusion There is a need to further develop and implement individually tailored information to glioma patients, both in consultations and patient-accessed EHR systems, which should have safe guards for sensitive information. Not all patients want to know it all, one size does not fit all., Funding Agencies|Linkoping University; County Council of Ostergotland (ALF); Medical Research Council of Southeast Sweden Research grant; NSC Research grant

Purpose Glioma patients have poor prognosis. The amount of detail of disease-related information patients wish to receive is not known. The aim of this study was to explore glioma patients experiences and preferences regarding receiving information on diagnosis and prognosis. Methods Semi-structured interviews were performed with patients diagnosed with glioma. The interviews were analysed by qualitative content analysis without predefined categories by two independent coders. Results Ten women and 15 men, with newly diagnosed grade II-IV glioma, age 25-76 years, were interviewed. Participants experience on diagnosis communication was either indirect, meaning they found out their diagnosis unintentionally, e.g., from their electronic health record (EHR) instead of from their doctor, this causing anxiety and feelings of abandonment, insufficiently tailored: lacking in many aspects or individualised and compassionate. Participants generally wanted to know "the truth" about diagnosis and prognosis, but what they meant varied; some desired full honest information to allow for autonomous choices, others preferred general information without details, and some wanted no bad news at all, only positive information. Participants disclosed vulnerability after receiving their diagnosis, being cast into the unknown. They expressed a need for better everyday practical information to help create some control. Supportive staff could reduce participants distress. Conclusion There is a need to further develop and implement individually tailored information to glioma patients, both in consultations and patient-accessed EHR systems, which should have safe guards for sensitive information. Not all patients want to know it all, one size does not fit all., Funding Agencies|Linkoping University; County Council of Ostergotland (ALF); Medical Research Council of Southeast Sweden Research grant; NSC Research grant

Simple Summary Glioblastoma (GBM) is one of the most common and most aggressive brain tumors with higher prevalence among men than women. Loss of chromosome Y (LOY) in the peripheral blood cells has been associated with increased risk of developing cancer. However, there is a lack of data about LOY in GBM tumor tissue and the potential impact on patients prognosis. Through droplet digital PCR (ddPCR) analysis of 10 markers spread throughout chromosome Y in 105 male GBM patients, we were able to identify deletion of SRY gene as a factor strongly correlating with reduced overall survival. This finding was later corroborated by the analysis of GBM gene expression data collected in TCGA, showing correlation between decreased SRY expression and shortened overall survival. 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 expressio, Funding Agencies|Erik, Karin and Gosta Selanders Foundation at Uppsala University Hospital; Swedish Cancer Foundation; ALF Grants; Region Ostergotland; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); LiU Cancer at Linkoping University; Lions Cancer Foundation

Simple Summary Glioblastoma (GBM) is one of the most common and most aggressive brain tumors with higher prevalence among men than women. Loss of chromosome Y (LOY) in the peripheral blood cells has been associated with increased risk of developing cancer. However, there is a lack of data about LOY in GBM tumor tissue and the potential impact on patients prognosis. Through droplet digital PCR (ddPCR) analysis of 10 markers spread throughout chromosome Y in 105 male GBM patients, we were able to identify deletion of SRY gene as a factor strongly correlating with reduced overall survival. This finding was later corroborated by the analysis of GBM gene expression data collected in TCGA, showing correlation between decreased SRY expression and shortened overall survival. 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 expressio, Funding Agencies|Erik, Karin and Gosta Selanders Foundation at Uppsala University Hospital; Swedish Cancer Foundation; ALF Grants; Region Ostergotland; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); LiU Cancer at Linkoping University; Lions Cancer Foundation

Simple Summary Glioblastoma (GBM) is one of the most common and most aggressive brain tumors with higher prevalence among men than women. Loss of chromosome Y (LOY) in the peripheral blood cells has been associated with increased risk of developing cancer. However, there is a lack of data about LOY in GBM tumor tissue and the potential impact on patients prognosis. Through droplet digital PCR (ddPCR) analysis of 10 markers spread throughout chromosome Y in 105 male GBM patients, we were able to identify deletion of SRY gene as a factor strongly correlating with reduced overall survival. This finding was later corroborated by the analysis of GBM gene expression data collected in TCGA, showing correlation between decreased SRY expression and shortened overall survival. 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 expressio, Funding Agencies|Erik, Karin and Gosta Selanders Foundation at Uppsala University Hospital; Swedish Cancer Foundation; ALF Grants; Region Ostergotland; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); LiU Cancer at Linkoping University; Lions Cancer Foundation

Purpose Glioma patients have poor prognosis. The amount of detail of disease-related information patients wish to receive is not known. The aim of this study was to explore glioma patients experiences and preferences regarding receiving information on diagnosis and prognosis. Methods Semi-structured interviews were performed with patients diagnosed with glioma. The interviews were analysed by qualitative content analysis without predefined categories by two independent coders. Results Ten women and 15 men, with newly diagnosed grade II-IV glioma, age 25-76 years, were interviewed. Participants experience on diagnosis communication was either indirect, meaning they found out their diagnosis unintentionally, e.g., from their electronic health record (EHR) instead of from their doctor, this causing anxiety and feelings of abandonment, insufficiently tailored: lacking in many aspects or individualised and compassionate. Participants generally wanted to know "the truth" about diagnosis and prognosis, but what they meant varied; some desired full honest information to allow for autonomous choices, others preferred general information without details, and some wanted no bad news at all, only positive information. Participants disclosed vulnerability after receiving their diagnosis, being cast into the unknown. They expressed a need for better everyday practical information to help create some control. Supportive staff could reduce participants distress. Conclusion There is a need to further develop and implement individually tailored information to glioma patients, both in consultations and patient-accessed EHR systems, which should have safe guards for sensitive information. Not all patients want to know it all, one size does not fit all., Funding Agencies|Linkoping University; County Council of Ostergotland (ALF); Medical Research Council of Southeast Sweden Research grant; NSC Research grant

Purpose Glioma patients have poor prognosis. The amount of detail of disease-related information patients wish to receive is not known. The aim of this study was to explore glioma patients experiences and preferences regarding receiving information on diagnosis and prognosis. Methods Semi-structured interviews were performed with patients diagnosed with glioma. The interviews were analysed by qualitative content analysis without predefined categories by two independent coders. Results Ten women and 15 men, with newly diagnosed grade II-IV glioma, age 25-76 years, were interviewed. Participants experience on diagnosis communication was either indirect, meaning they found out their diagnosis unintentionally, e.g., from their electronic health record (EHR) instead of from their doctor, this causing anxiety and feelings of abandonment, insufficiently tailored: lacking in many aspects or individualised and compassionate. Participants generally wanted to know "the truth" about diagnosis and prognosis, but what they meant varied; some desired full honest information to allow for autonomous choices, others preferred general information without details, and some wanted no bad news at all, only positive information. Participants disclosed vulnerability after receiving their diagnosis, being cast into the unknown. They expressed a need for better everyday practical information to help create some control. Supportive staff could reduce participants distress. Conclusion There is a need to further develop and implement individually tailored information to glioma patients, both in consultations and patient-accessed EHR systems, which should have safe guards for sensitive information. Not all patients want to know it all, one size does not fit all., Funding Agencies|Linkoping University; County Council of Ostergotland (ALF); Medical Research Council of Southeast Sweden Research grant; NSC Research grant

Simple Summary Glioblastoma (GBM) is one of the most common and most aggressive brain tumors with higher prevalence among men than women. Loss of chromosome Y (LOY) in the peripheral blood cells has been associated with increased risk of developing cancer. However, there is a lack of data about LOY in GBM tumor tissue and the potential impact on patients prognosis. Through droplet digital PCR (ddPCR) analysis of 10 markers spread throughout chromosome Y in 105 male GBM patients, we were able to identify deletion of SRY gene as a factor strongly correlating with reduced overall survival. This finding was later corroborated by the analysis of GBM gene expression data collected in TCGA, showing correlation between decreased SRY expression and shortened overall survival. 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 expressio, Funding Agencies|Erik, Karin and Gosta Selanders Foundation at Uppsala University Hospital; Swedish Cancer Foundation; ALF Grants; Region Ostergotland; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); LiU Cancer at Linkoping University; Lions Cancer Foundation

Purpose Glioma patients have poor prognosis. The amount of detail of disease-related information patients wish to receive is not known. The aim of this study was to explore glioma patients experiences and preferences regarding receiving information on diagnosis and prognosis. Methods Semi-structured interviews were performed with patients diagnosed with glioma. The interviews were analysed by qualitative content analysis without predefined categories by two independent coders. Results Ten women and 15 men, with newly diagnosed grade II-IV glioma, age 25-76 years, were interviewed. Participants experience on diagnosis communication was either indirect, meaning they found out their diagnosis unintentionally, e.g., from their electronic health record (EHR) instead of from their doctor, this causing anxiety and feelings of abandonment, insufficiently tailored: lacking in many aspects or individualised and compassionate. Participants generally wanted to know "the truth" about diagnosis and prognosis, but what they meant varied; some desired full honest information to allow for autonomous choices, others preferred general information without details, and some wanted no bad news at all, only positive information. Participants disclosed vulnerability after receiving their diagnosis, being cast into the unknown. They expressed a need for better everyday practical information to help create some control. Supportive staff could reduce participants distress. Conclusion There is a need to further develop and implement individually tailored information to glioma patients, both in consultations and patient-accessed EHR systems, which should have safe guards for sensitive information. Not all patients want to know it all, one size does not fit all., Funding Agencies|Linkoping University; County Council of Ostergotland (ALF); Medical Research Council of Southeast Sweden Research grant; NSC Research grant

Simple Summary Glioblastoma (GBM) is one of the most common and most aggressive brain tumors with higher prevalence among men than women. Loss of chromosome Y (LOY) in the peripheral blood cells has been associated with increased risk of developing cancer. However, there is a lack of data about LOY in GBM tumor tissue and the potential impact on patients prognosis. Through droplet digital PCR (ddPCR) analysis of 10 markers spread throughout chromosome Y in 105 male GBM patients, we were able to identify deletion of SRY gene as a factor strongly correlating with reduced overall survival. This finding was later corroborated by the analysis of GBM gene expression data collected in TCGA, showing correlation between decreased SRY expression and shortened overall survival. 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 expressio, Funding Agencies|Erik, Karin and Gosta Selanders Foundation at Uppsala University Hospital; Swedish Cancer Foundation; ALF Grants; Region Ostergotland; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); LiU Cancer at Linkoping University; Lions Cancer Foundation

Standard treatment for glioblastoma (GBM) patients is surgery and radiochemotherapy (RCT) with temozolomide (TMZ). TMZ is a substrate for ABCB1, a transmembrane drug transporter. It has been suggested that survival for GBM patients receiving TMZ is influenced by different single-nucleotide variants (SNV) of ABCB1. We therefore examined SNV:s of ABCB1, namely 1199Gamp;gt;A, 1236Camp;gt;T, 2677Gamp;gt;T/A, and 3435Camp;gt;T and correlated to survival for GBM patients receiving RCT. In a pilot cohort (97 patients) a significant correlation to survival was found for SNV 1199Gamp;gt;A, with median OS for variant G/G patients being 18.2 months versus 11.5 months for A/G (p = 0.012). We found no correlation to survival for the other SNV:s. We then expanded the cohort to 179 patients (expanded cohort) and also included a confirmatory cohort (49 patients) focusing on SNV 1199Gamp;gt;A. Median OS for G/G versus A/G plus A/A was 15.7 and 11.5 months, respectively (p = 0.085) for the expanded cohort and 13.8 versus 16.8 months (p = 0.19) for the confirmatory. In conclusion, in patients with GBM receiving RCT with TMZ, no correlation with survival was found for the SNV:s 1236Camp;gt;T, 2677Gamp;gt;T/A, and 3435Camp;gt;T of ABCB1. Although the SNV 1199Gamp;gt;A might have some impact, a clinically significant role could not be confirmed., Funding Agencies|Swedish Cancer SocietySwedish Cancer Society; County Council of ostergotland; South-East Sweden FORSS research grant; LiUCancer