美国圣裘德儿童研究医院Jinghui Zhang研究组取得最新进展。他们使用GenomePaint探索癌症的编码和非编码变体。相关论文发表在2021年1月11日出版的《癌细胞》杂志上。

GenomePaint（https://genomepaint.stjude.cloud/）是一个交互式可视化平台，包括肿瘤样本的全基因组、全外显子组、转录组和表观基因组数据。它的设计捕捉了DNA变异与RNA表达之间的相互关系，支持深入探索单个癌症基因组和整个队列。调节性非编码变体可以与编码变体一起进行检查和分析，通过检查癌细胞系的3D基因组数据进一步探索其功能影响。

此外，GenomePaint将突变和表达模式与患者预后相关联，并支持自定义数据上传。他们使用GenomePaint揭示了异常剪接，该剪接破坏了CREBBP的RING结构域，通过在B系急性淋巴细胞白血病中复制NOTCH1-MYC增强子来发现MYC癌基因的顺式激活，并探讨了成年胶质母细胞瘤中EGFR的肿瘤内和肿瘤间异质性。

这些例子表明，由GenomePaint支持的对单个癌症基因组的深入多组学探索，可以为后续验证提供生物学见解。

附：英文原文

Title: Exploration of Coding and Non-coding Variants in Cancer Using GenomePaint

Author: Xin Zhou, Jian Wang, Jaimin Patel, Marc Valentine, Ying Shao, Scott Newman, Edgar Sioson, Liqing Tian, Yu Liu, Samuel W. Brady, Diane Flasch, Xiaotu Ma, Yanling Liu, Robin Paul, Michael N. Edmonson, Michael C. Rusch, Chunliang Li, Suzanne J. Baker, John Easton, Jinghui Zhang

Issue&Volume: 2021/01/11

Abstract: GenomePaint (https://genomepaint.stjude.cloud/) is an interactive visualization platform for whole-genome, whole-exome, transcriptome,and epigenomic data of tumor samples. Its design captures the inter-relatedness betweenDNA variations and RNA expression, supporting in-depth exploration of both individualcancer genomes and full cohorts. Regulatory non-coding variants can be inspected andanalyzed along with coding variants, and their functional impact further exploredby examining 3D genome data from cancer cell lines. Further, GenomePaint correlatesmutation and expression patterns with patient outcomes, and supports custom data upload.We used GenomePaint to unveil aberrant splicing that disrupts the RING domain of CREBBP, discover cis activation of the MYC oncogene by duplication of the NOTCH1-MYC enhancer in B-lineage acute lymphoblasticleukemia, and explore the inter- and intra-tumor heterogeneity at EGFR in adult glioblastomas. These examples demonstrate that deep multi-omics explorationof individual cancer genomes enabled by GenomePaint can lead to biological insightsfor follow-up validation.

DOI: 10.1016/j.ccell.2020.12.011

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30659-0