研究揭示犬和人胶质瘤发生的分子异同
2020-02-14   阅读:587   来源:细胞

2020年2月10日,《癌细胞》发表了美国杰克逊实验室Roel G.W. Verhaak研究组的最新成果,他们对犬类和人类的自发型胶质瘤进行了突变水平的比较研究。

研究人员比较了犬神经胶质瘤与人类儿童和成人神经胶质瘤的分子谱,以表征神经胶质瘤发生中进化保守的哺乳动物突变过程。利用83个犬神经胶质瘤的全基因组、外显子组、转录组和甲基化测序,研究人员发现犬和人胶质瘤之间存在相同的改变,例如受体酪氨酸激酶、TP53和细胞周期途径以及IDH1 R132。犬神经胶质瘤与人小儿神经胶质瘤在稳健的非整倍性、突变率、突变的相对时机和DNA甲基化模式方面显示出高度相似性。这一跨物种比较基因组分析为神经胶质瘤的病因和引起神经胶质瘤的体细胞变化的时间提供了独特见解。
 
据悉,伴侣犬的散发性胶质瘤为致瘤机制与宿主环境之间的相互作用提供了一个研究机会。
 
附:英文原文
 
Title: Comparative Molecular Life History of Spontaneous Canine and Human Gliomas

Author: Samirkumar B. Amin, Kevin J. Anderson, C. Elizabeth Boudreau, Emmanuel Martinez-Ledesma, Emre Kocakavuk, Kevin C. Johnson, Floris P. Barthel, Frederick S. Varn, Cynthia Kassab, Xiaoyang Ling, Hoon Kim, Mary Barter, Ching C. Lau, Chew Yee Ngan, Margaret Chapman, Jennifer W. Koehler, James P. Long, Andrew D. Miller, C. Ryan Miller, Brian F. Porter, Daniel R. Rissi, Christina Mazcko, Amy K. LeBlanc, Peter J. Dickinson, Rebecca A. Packer, Amanda R. Taylor, John H. Rossmeisl, Kevin D. Woolard, Amy B. Heimberger, Jonathan M. Levine, Roel G.W. Verhaak

Issue&Volume: 2020/02/10

Abstract: Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenicmechanisms and host environment. We compared the molecular profiles of canine gliomaswith those of human pediatric and adult gliomas to characterize evolutionarily conservedmammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome,and methylation sequencing of 83 canine gliomas, we found alterations shared betweencanine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robustaneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns.Our cross-species comparative genomic analysis provides unique insights into gliomaetiology and the chronology of glioma-causing somatic alterations.

DOI: 10.1016/j.ccell.2020.01.004

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