必需的基因组不稳定性抑制基因可鉴定潜在的人类肿瘤抑制因子。
Essential genome instability suppressing genes identify potential human tumor suppressors.
机构信息
Ludwig Institute for Cancer Research, University of California San Diego School of Medicine, La Jolla, CA 92093-0669.
Bioinformatics Multidisciplinary Environment, Instituto Metrópole Digital-Universidade Federal do Rio Grande do Norte, Natal, Brazil 59082-180.
出版信息
Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17377-17382. doi: 10.1073/pnas.1906921116. Epub 2019 Aug 13.
Gross Chromosomal Rearrangements (GCRs) play an important role in human diseases, including cancer. Although most of the nonessential Genome Instability Suppressing (GIS) genes in are known, the essential genes in which mutations can cause increased GCR rates are not well understood. Here 2 GCR assays were used to screen a targeted collection of temperature-sensitive mutants to identify mutations that caused increased GCR rates. This identified 94 essential GIS (eGIS) genes in which mutations cause increased GCR rates and 38 candidate eGIS genes that encode eGIS1 protein-interacting or family member proteins. Analysis of TCGA data using the human genes predicted to encode the proteins and protein complexes implicated by the eGIS genes revealed a significant enrichment of mutations affecting predicted human eGIS genes in 10 of the 16 cancers analyzed.
染色体大片段重排（GCRs）在人类疾病中起着重要作用，包括癌症。尽管已经确定了 中大多数非必需的基因组不稳定性抑制（GIS）基因，但导致 GCR 率增加的突变的必需基因还不是很清楚。在这里，我们使用两种 GCR 测定法筛选了一个靶向收集的温度敏感突变体，以鉴定导致 GCR 率增加的突变。这确定了 94 个导致 GCR 率增加的必需 GIS（eGIS）基因，以及 38 个候选 eGIS 基因，这些基因编码 eGIS1 蛋白相互作用或家族成员蛋白。使用 TCGA 数据对预测的人类基因进行分析，这些基因编码的蛋白复合物涉及到 eGIS 基因，结果显示在分析的 16 种癌症中的 10 种中，存在显著富集的影响预测人类 eGIS 基因的突变。
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