美国麻省理工学院和哈佛大学Gad Getz研究组发现慢性淋巴细胞白血病 (CLL)的分子图谱及其对预后的影响。这一研究成果发表在2022年8月4日出版的国际学术期刊《自然—遗传学》上。
他们专注于CLL，这是一种具有可变自然史的 B 细胞肿瘤，通常分为两种亚型，以免疫球蛋白基因 (IGHV) 重链可变区的体细胞突变程度区分。为了构建“CLL 图”，他们整合了来自 1,148 名患者的基因组、转录组和表观基因组数据。他们确定了 202 个 CLL 候选遗传驱动因素（109 个新），并改进了 IGHV 亚型的表征，揭示了不同的基因组景观和白血病发生轨迹。新基因表达亚型的发现进一步细分了这种肿瘤，并被证明是独立的预后因素。临床结果与遗传、表观遗传和基因表达特征的组合相关，进一步推进了他们的预后范式。
总体而言，这项工作揭示了对 CLL 肿瘤发生和预后的新见解。
据介绍，癌症表征的最新进展一直显示出明显的异质性，阻碍了每种恶性肿瘤的综合分子和临床图谱的完成。
附：英文原文
Title: Molecular map of chronic lymphocytic leukemia and its impact on outcome
Author: Knisbacher, Binyamin A., Lin, Ziao, Hahn, Cynthia K., Nadeu, Ferran, Duran-Ferrer, Mart, Stevenson, Kristen E., Tausch, Eugen, Delgado, Julio, Barbera-Mourelle, Alex, Taylor-Weiner, Amaro, Bousquets-Muoz, Pablo, Diaz-Navarro, Ander, Dunford, Andrew, Anand, Shankara, Kretzmer, Helene, Gutierrez-Abril, Jesus, Lpez-Tamargo, Sara, Fernandes, Stacey M., Sun, Clare, Sivina, Mariela, Rassenti, Laura Z., Schneider, Christof, Li, Shuqiang, Parida, Laxmi, Meissner, Alexander, Aguet, Franois, Burger, Jan A., Wiestner, Adrian, Kipps, Thomas J., Brown, Jennifer R., Hallek, Michael, Stewart, Chip, Neuberg, Donna S., Martn-Subero, Jos I., Puente, Xose S., Stilgenbauer, Stephan, Wu, Catherine J., Campo, Elias, Getz, Gad
Issue&Volume: 2022-08-04
Abstract: Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the ‘CLL map,’ we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. Discovery of new gene expression subtypes further subcategorized this neoplasm and proved to be independent prognostic factors. Clinical outcomes were associated with a combination of genetic, epigenetic and gene expression features, further advancing our prognostic paradigm. Overall, this work reveals fresh insights into CLL oncogenesis and prognostication.
DOI: 10.1038/s41588-022-01140-w
Source: https://www.nature.com/articles/s41588-022-01140-w
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
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
