Sturgill Ian R, Raab Jesse R, Hoadley Katherine A
Bioinformatics and Computational Biology Curriculum, Department of Genetics, University of North Carolina at Chapel Hill, 116 Manning Drive, Chapel Hill, NC 27599, USA.
Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 116 Manning Drive, Chapel Hill, NC 27599, USA.
NAR Cancer. 2024 Nov 15;6(4):zcae045. doi: 10.1093/narcan/zcae045. eCollection 2024 Dec.
Aberrant expression of the ( associated protein 1) tumor suppressor gene is a prominent risk factor for several tumor types and is important in tumor evolution and progression. Here we performed integrated multi-omics analyses using data from The Cancer Genome Atlas for 33 cancer types and over 10 000 individuals to identify alterations leading to disruption. We combined existing variant calls and new calls derived from a local realignment pipeline across multiple independent variant callers, increasing somatic variant detection by 41% from 182 to 257, including 11 indels ≥40 bp. The expanded detection of mutations highlights the power of new tools to uncover longer indels and impactful mutations. We developed an expression-based activity score and identified a transcriptional profile associated with disruption in cancer. has been proposed to play a critical role in controlling tumor plasticity and normal cell fate. Leveraging human and mouse liver datasets, loss in normal cells resulted in lower activity scores and lower scores were associated with a less-differentiated phenotype in embryonic cells. Together, our expanded mutant samples revealed a transcriptional signature in cancer cells, supporting 's influences on cellular plasticity and cell identity maintenance.
（相关蛋白1）肿瘤抑制基因的异常表达是多种肿瘤类型的一个突出风险因素，在肿瘤的发生发展过程中起着重要作用。在此，我们使用来自癌症基因组图谱（The Cancer Genome Atlas）的33种癌症类型和超过10000名个体的数据进行了综合多组学分析，以确定导致（相关蛋白1）功能破坏的改变。我们将现有的变异检测结果与通过跨多个独立变异检测工具的局部重排流程得出的新检测结果相结合，使体细胞变异检测数量从182个增加到257个，增幅达41%，其中包括11个长度≥40 bp的插入缺失。对突变检测范围的扩大凸显了新工具在发现更长插入缺失和有影响的突变方面的强大作用。我们开发了一种基于表达的（相关蛋白1）活性评分，并确定了一种与癌症中（相关蛋白1）功能破坏相关的转录谱。有人提出（相关蛋白1）在控制肿瘤可塑性和正常细胞命运方面起着关键作用。利用人类和小鼠肝脏数据集，正常细胞中的（相关蛋白1）缺失导致活性评分降低，而较低的评分与胚胎细胞中分化程度较低的表型相关。总之，我们扩大后的（相关蛋白1）突变样本揭示了癌细胞中的一种转录特征，支持了（相关蛋白1）对细胞可塑性和细胞身份维持的影响。
