由英国剑桥大学Elizabeth P. Murchison领导的国际团队，探究了一个古老、可传播的癌症谱系的体细胞进化和全球扩张。相关论文于2019年8月2日发表于国际顶尖学术期刊《科学》上。

研究人员从546个CTVT外显子中建立了一个时间分辨的发展史，描述该谱系的全球扩张。通过检查突变暴露的变异，研究人员确定了一种高度背景特异性的突变过程，该过程在癌症进化的早期起作用但随后消失，将紫外线诱变与肿瘤纬度相关联，并描述具有内源性突变过程的遗传性过度活跃的肿瘤。CTVT几乎没有显示正在进行的阳性选择，只有必需基因才能检测到阴性选择。研究人员说明了长寿克隆生物如何捕捉诱变环境变化，表明中性基因漂变是长期癌症发展的主要特点。

研究人员表示，犬传染性性病肿瘤(CTVT)是几千年前出现的癌症谱系，通过细胞转移在宿主之间“转移”而存活下来，这种癌症的体细胞突变记录了其系统发育和进化史。

附：英文原文

Title: Somatic evolution and global expansion of an ancient transmissible cancer lineage

Author: Adrian Baez-Ortega, Kevin Gori, Andrea Strakova, Janice L. Allen, Karen M. Allum, Leontine Bansse-Issa, Thinlay N. Bhutia, Jocelyn L. Bisson, Cristóbal Briceo, Artemio Castillo Domracheva, Anne M. Corrigan, Hugh R. Cran, Jane T. Crawford, Eric Davis, Karina F. de Castro, Andrigo B. de Nardi, Anna P. de Vos, Laura Delgadillo Keenan, Edward M. Donelan, Adela R. Espinoza Huerta, Ibikunle A. Faramade, Mohammed Fazil, Eleni Fotopoulou, Skye N. Fruean, Fanny Gallardo-Arrieta, Olga Glebova, Pagona G. Gouletsou, Rodrigo F. Hfelin Manrique, Joaquim J. G. P. Henriques, Rodrigo S. Horta, Natalia Ignatenko, Yaghouba Kane, Cathy King, Debbie Koenig, Ada Krupa, Steven J. Kruzeniski, Young-Mi Kwon, Marta Lanza-Perea, Mihran Lazyan, Adriana M. Lopez Quintana, Thibault Losfelt, Gabriele Marino, Simón Martínez Castaeda, Mayra F. Martínez-López, Michael Meyer, Edward J. Migneco, Berna Nakanwagi, Karter B. Neal, Winifred Neunzig, Máire Ní Leathlobhair, Sally J. Nixon, Antonio Ortega-Pacheco, Francisco Pedraza-Ordoez, Maria C. Peleteiro, Katherine Polak, Ruth J. Pye, John F. Reece, Jose Rojas Gutierrez, Haleema Sadia, Sheila K. Schmeling, Olga Shamanova, Alan G. Sherlock, Maximilian Stammnitz, Audrey E. Steenland-Smit, Alla Svitich, Lester J. Tapia Martínez, Ismail Thoya Ngoka, Cristian G. Torres, Elizabeth M. Tudor, Mirjam G. van der Wel, Bogdan A. Vi??laru, Sevil A. Vural, Oliver Walkinton, Jinhong Wang, Alvaro S. Wehrle-Martinez, Sophie A. E. Widdowson, Michael R. Stratton, Ludmil B. Alexandrov, Iñigo Martincorena, Elizabeth P. Murchison

Issue&Volume: Vol 365 Issue 6452

Abstract: The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage’s worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer’s evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

DOI: 10.1126/science.aau9923

Source: https://science.sciencemag.org/content/365/6452/eaau9923