小柯机器人

英国牛津大学Anna Schuh团队近期取得重要工作进展，他们通过对慢性淋巴细胞白血病进行全基因组测序，确定了具有不同生物学和临床特征的亚组。相关论文2022年11月4日在线发表于《自然—遗传学》杂志上。

研究人员报告了485名慢性淋巴细胞白血病患者的全基因组测序，这些患者参加了英国10万基因组计划的临床试验。他们确定了重复编码和非编码基因突变的扩展目录，该目录代表了未来研究的来源，并提供了结构变异、拷贝数变化和全基因组特征（包括端粒长度、突变特征和基因组复杂性）最完整的高分辨率图谱。

研究人员证明了这些特征与临床结果的关系，并表明186种不同复发性基因组改变的整合，定义了与治疗反应相关的五个基因组亚群，从而改进了传统的结果预测。虽然需要独立验证，但这一发现强调了全基因组测序在慢性淋巴细胞白血病未来风险分层中的应用潜力。

据介绍，在预测癌症患者临床结果方面，全基因组与靶向驱动因素分析相比哪个更有价值，目前还存在争议。

附：英文原文

Title: Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features

Author: Robbe, Pauline, Ridout, Kate E., Vavoulis, Dimitrios V., Drau, Helene, Kinnersley, Ben, Denny, Nicholas, Chubb, Daniel, Appleby, Niamh, Cutts, Anthony, Cornish, Alex J., Lopez-Pascua, Laura, Clifford, Ruth, Burns, Adam, Stamatopoulos, Basile, Cabes, Maite, Alsolami, Reem, Antoniou, Pavlos, Oates, Melanie, Cavalieri, Doriane, Gibson, Jane, Prabhu, Anika V., Schwessinger, Ron, Jennings, Daisy, James, Terena, Maheswari, Uma, Duran-Ferrer, Mart, Carninci, Piero, Knight, Samantha J. L., Mnsson, Robert, Hughes, Jim, Davies, James, Ross, Mark, Bentley, David, Strefford, Jonathan C., Devereux, Stephen, Pettitt, Andrew R., Hillmen, Peter, Caulfield, Mark J., Houlston, Richard S., Martn-Subero, Jos I., Schuh, Anna

Issue&Volume: 2022-11-04

Abstract: The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia.

DOI: 10.1038/s41588-022-01211-y

Source: https://www.nature.com/articles/s41588-022-01211-y

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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