Chromosome 7 Gain Compensates for Chromosome 10 Loss in Glioma.
| Autor: | Nair NU; Cancer Data Science Laboratory, Computational Precision Oncology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Schäffer AA; Cancer Data Science Laboratory, Computational Precision Oncology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Gertz EM; Cancer Data Science Laboratory, Computational Precision Oncology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Cheng K; Cancer Data Science Laboratory, Computational Precision Oncology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.; MSD, Beijing, China., Zerbib J; Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel., Sahu AD; Comprehensive Cancer Center, The University of New Mexico, Albuquerque, New Mexico., Leor G; Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel., Shulman ED; Cancer Data Science Laboratory, Computational Precision Oncology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Aldape KD; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Ben-David U; Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel., Ruppin E; Cancer Data Science Laboratory, Computational Precision Oncology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. |
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| Jazyk: | angličtina |
| Zdroj: | Cancer research [Cancer Res] 2024 Oct 15; Vol. 84 (20), pp. 3464-3477. |
| DOI: | 10.1158/0008-5472.CAN-24-1366 |
| Abstrakt: | The co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers. This phenomenon has been investigated since the late 1980s without resolution. Expanding beyond previous gene-centric studies, we investigated the co-occurrence in a genome-wide manner, taking an evolutionary perspective. Mining of large-scale tumor aneuploidy data confirmed the previous finding of a small-scale longitudinal study that the most likely order is chromosome 10 loss, followed by chromosome 7 gain. Extensive analysis of genomic and transcriptomic data from both patients and cell lines revealed that this co-occurrence can be explained by functional rescue interactions that are highly enriched on chromosome 7, which could potentially compensate for any detrimental consequences arising from the loss of chromosome 10. Transcriptomic data from various normal, noncancerous human brain tissues were analyzed to assess which tissues may be most predisposed to tolerate compensation of chromosome 10 loss by chromosome 7 gain. The analysis indicated that the preexisting transcriptomic states in the cortex and frontal cortex, where gliomas arise, are more favorable than other brain regions for compensation by rescuer genes that are active on chromosome 7. Collectively, these findings suggest that the phenomenon of chromosome 10 loss and chromosome 7 gain in gliomas is orchestrated by a complex interaction of many genes residing within these two chromosomes and provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain. Significance: Increased expression of multiple rescuer genes on the gained chromosome 7 could compensate for the downregulation of several vulnerable genes on the lost chromosome 10, resolving the long-standing mystery of this frequent co-occurrence in gliomas. (©2024 American Association for Cancer Research.) |
| Databáze: | MEDLINE |
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