Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome
Loss of the Y chromosome (LoY) is frequently observed in somatic cells of elderly men. However, LoY is highly increased in tumor tissue and correlates with an overall worse prognosis. The underlying causes and downstream effects of LoY are widely unknown. Therefore, we analyzed genomic and transcrip...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023000727 |
| _version_ | 1827577650214862848 |
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| author | Philipp Müller Oscar Velazquez Camacho Ali M. Yazbeck Christina Wölwer Weiwei Zhai Johannes Schumacher Dominik Heider Reinhard Buettner Alexander Quaas Axel M. Hillmer |
| author_facet | Philipp Müller Oscar Velazquez Camacho Ali M. Yazbeck Christina Wölwer Weiwei Zhai Johannes Schumacher Dominik Heider Reinhard Buettner Alexander Quaas Axel M. Hillmer |
| author_sort | Philipp Müller |
| collection | DOAJ |
| description | Loss of the Y chromosome (LoY) is frequently observed in somatic cells of elderly men. However, LoY is highly increased in tumor tissue and correlates with an overall worse prognosis. The underlying causes and downstream effects of LoY are widely unknown. Therefore, we analyzed genomic and transcriptomic data of 13 cancer types (2375 patients) and classified tumors of male patients according to loss or retain of the Y chromosome (LoY or RoY, average LoY fraction: 0.46). The frequencies of LoY ranged from almost absence (glioblastoma, glioma, thyroid carcinoma) to 77% (kidney renal papillary cell carcinoma). Genomic instability, aneuploidy, and mutation burden were enriched in LoY tumors. In addition, we found more frequently in LoY tumors the gate keeping tumor suppressor gene TP53 mutated in three cancer types (colon adenocarcinoma, head and neck squamous carcinoma, lung adenocarcinoma) and oncogenes MET, CDK6, KRAS, and EGFR amplified in multiple cancer types. On the transcriptomic level, we observed MMP13, known to be involved in invasion, to be up-regulated in LoY of three adenocarcinomas and down-regulation of the tumor suppressor gene GPC5 in LoY of three cancer types. Furthermore, we found enrichment of a smoking-related mutation signature in LoY tumors of head and neck and lung cancer. Strikingly, we observed a correlation between cancer type-specific sex bias in incidence rates and frequencies of LoY, in line with the hypothesis that LoY increases cancer risk in males. Overall, LoY is a frequent phenomenon in cancer that is enriched in genomically unstable tumors. It correlates with genomic features beyond the Y chromosome and might contribute to higher incidence rates in males. |
| first_indexed | 2024-03-08T21:30:49Z |
| format | Article |
| id | doaj.art-14c0882d1e4b492da923087027d667f5 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:30:49Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-14c0882d1e4b492da923087027d667f52023-12-21T07:31:04ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012115731583Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosomePhilipp Müller0Oscar Velazquez Camacho1Ali M. Yazbeck2Christina Wölwer3Weiwei Zhai4Johannes Schumacher5Dominik Heider6Reinhard Buettner7Alexander Quaas8Axel M. Hillmer9University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Cologne, GermanyUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Cologne, GermanyUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Cologne, GermanyUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Cologne, GermanyKey Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaInstitute of Human Genetics, University Hospital of Marburg, Marburg, GermanyDepartment of Data Science in Biomedicine, Faculty of Mathematics and Computer Science, Philipps-University of Marburg, GermanyUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Cologne, GermanyUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Cologne, Germany; Cologne Group of Sex-specific Oncobiology (CGSO), GermanyUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Cologne, Germany; Cologne Group of Sex-specific Oncobiology (CGSO), Germany; University of Cologne, Center for Molecular Medicine Cologne, Cologne, Germany; Correspondence to: Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Kerpener Str. 62, 50937 Cologne, Germany. fax: +49 221 4786360Loss of the Y chromosome (LoY) is frequently observed in somatic cells of elderly men. However, LoY is highly increased in tumor tissue and correlates with an overall worse prognosis. The underlying causes and downstream effects of LoY are widely unknown. Therefore, we analyzed genomic and transcriptomic data of 13 cancer types (2375 patients) and classified tumors of male patients according to loss or retain of the Y chromosome (LoY or RoY, average LoY fraction: 0.46). The frequencies of LoY ranged from almost absence (glioblastoma, glioma, thyroid carcinoma) to 77% (kidney renal papillary cell carcinoma). Genomic instability, aneuploidy, and mutation burden were enriched in LoY tumors. In addition, we found more frequently in LoY tumors the gate keeping tumor suppressor gene TP53 mutated in three cancer types (colon adenocarcinoma, head and neck squamous carcinoma, lung adenocarcinoma) and oncogenes MET, CDK6, KRAS, and EGFR amplified in multiple cancer types. On the transcriptomic level, we observed MMP13, known to be involved in invasion, to be up-regulated in LoY of three adenocarcinomas and down-regulation of the tumor suppressor gene GPC5 in LoY of three cancer types. Furthermore, we found enrichment of a smoking-related mutation signature in LoY tumors of head and neck and lung cancer. Strikingly, we observed a correlation between cancer type-specific sex bias in incidence rates and frequencies of LoY, in line with the hypothesis that LoY increases cancer risk in males. Overall, LoY is a frequent phenomenon in cancer that is enriched in genomically unstable tumors. It correlates with genomic features beyond the Y chromosome and might contribute to higher incidence rates in males.http://www.sciencedirect.com/science/article/pii/S2001037023000727Loss of YY chromosomeAneuploidyTCGAPan-Cancer |
| spellingShingle | Philipp Müller Oscar Velazquez Camacho Ali M. Yazbeck Christina Wölwer Weiwei Zhai Johannes Schumacher Dominik Heider Reinhard Buettner Alexander Quaas Axel M. Hillmer Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome Computational and Structural Biotechnology Journal Loss of Y Y chromosome Aneuploidy TCGA Pan-Cancer |
| title | Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome |
| title_full | Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome |
| title_fullStr | Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome |
| title_full_unstemmed | Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome |
| title_short | Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome |
| title_sort | why loss of y a pan cancer genome analysis of tumors with loss of y chromosome |
| topic | Loss of Y Y chromosome Aneuploidy TCGA Pan-Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023000727 |
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