Nair Nishanth Ulhas, Schäffer Alejandro A, Gertz E Michael, Cheng Kuoyuan, Zerbib Johanna, Sahu Avinash Das, Leor Gil, Shulman Eldad D, Aldape Kenneth D, Ben-David Uri, Ruppin Eytan
bioRxiv. 2024 Jan 22:2024.01.17.576103. doi: 10.1101/2024.01.17.576103.
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, a phenomenon that has been investigated without resolution since the late 1980s. Expanding beyond previous gene-centric studies, we investigate the co-occurrence in a genome-wide manner taking an evolutionary perspective. First, by mining large tumor aneuploidy data, we predict that the more likely order is 10 loss followed by 7 gain. Second, by analyzing extensive genomic and transcriptomic data from both patients and cell lines, we find that this co-occurrence can be explained by functional rescue interactions that are highly enriched on 7, which can possibly compensate for any detrimental consequences arising from the loss of 10. Finally, by analyzing transcriptomic data from normal, non-cancerous, human brain tissues, we provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.
胶质瘤中10号染色体缺失和7号染色体增加的同时出现是人类癌症中最常见的缺失-增加共非整倍体对，自20世纪80年代末以来，这一现象一直未得到解决。超越以往以基因为中心的研究，我们从进化的角度以全基因组的方式研究这种共现现象。首先，通过挖掘大量肿瘤非整倍体数据，我们预测更可能的顺序是先发生10号染色体缺失，然后是7号染色体增加。其次，通过分析来自患者和细胞系的大量基因组和转录组数据，我们发现这种共现可以由在7号染色体上高度富集的功能拯救相互作用来解释，这可能补偿了10号染色体缺失产生的任何有害后果。最后，通过分析来自正常、非癌性人类脑组织的转录组数据，我们给出了这种共现为何优先发生在起源于大脑某些区域的癌症中的一个合理原因。
