英国弗朗西斯•克里克研究所Peter Van Loo和欧洲分子生物学实验室生物信息学研究所Moritz Gerstung合作揭示了2658种癌症的进化史。2020年2月6日，国际学术期刊《自然》在线发表了这一成果。
作为国际癌症基因组联合会（ICGC）和癌症基因组图谱（TCGA）全基因组泛癌基因分析（PCAWG）联合会的一部分，研究人员对2658种癌症进行了全基因组测序分析，并对癌症突变过程的生命史和进化史进行重构以及促使38种癌症发生的突变序列进行了探究。早期肿瘤的特征是一组受限驱动基因的突变和特定拷贝数的增加，例如胶质母细胞瘤中7号染色体的三体性和髓母细胞瘤中17q的等染色体。在40％的样品中，随着肿瘤演化进程其突变谱发生了显著变化。近四倍驱动基因的多样性和基因组不稳定性增加是晚期癌症的特征。拷贝数变化通常发生在不稳定的有丝分裂过程中，同时导致染色体片段化。时序分析表明，驱动突变通常要比诊断早很多年，甚至几十年。这些结果揭示了癌症的发展轨迹，并为早期癌症诊断提供了机会。
据介绍，癌症是通过体细胞进化而形成的。单细胞的活检测序数据代表了这一过程的概况，可以揭示特定基因组畸变的时间以及突变过程变化的影响。
附：英文原文
Title: The evolutionary history of 2,658 cancers
Author: Moritz Gerstung, Clemency Jolly, Ignaty Leshchiner, Stefan C. Dentro, Santiago Gonzalez, Daniel Rosebrock, Thomas J. Mitchell, Yulia Rubanova, Pavana Anur, Kaixian Yu, Maxime Tarabichi, Amit Deshwar, Jeff Wintersinger, Kortine Kleinheinz, Ignacio Vzquez-Garca, Kerstin Haase, Lara Jerman, Subhajit Sengupta, Geoff Macintyre, Salem Malikic, Nilgun Donmez, Dimitri G. Livitz, Marek Cmero, Jonas Demeulemeester, Steven Schumacher, Yu Fan, Xiaotong Yao, Juhee Lee, Matthias Schlesner, Paul C. Boutros, David D. Bowtell, Hongtu Zhu, Gad Getz, Marcin Imielinski, Rameen Beroukhim, S. Cenk Sahinalp, Yuan Ji, Martin Peifer, Florian Markowetz, Ville Mustonen, Ke Yuan, Wenyi Wang, Quaid D. Morris, Paul T. Spellman, David C. Wedge, Peter Van Loo
Issue&Volume: 2020-02-06
Abstract: Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
DOI: 10.1038/s41586-019-1907-7
Source: https://www.nature.com/articles/s41586-019-1907-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
