来自加拿大坎贝尔家族癌症研究所、多伦多大学等机构的研究人员发现肿瘤内的异质性肿瘤细胞的功能多样性可能不能仅用遗传差异来解释,表观遗传等因素也会导致肿瘤细胞产生差异。

-2013年2月1日《科学》

中文翻译


【题目】不同的癌细胞增殖动力学影响结直肠癌对化疗的反应

【译文】在肿瘤发育过程中,肿瘤通过遗传多样性的亚克隆进化产生异质性。然而,单遗传克隆内的细胞是否具有相同的功能还不清楚。本文通过DNA拷贝数变异(CNA)谱、DNA测序和慢病毒株系跟踪,以及在小鼠体内进行连续异种移植传代培养等方法,来研究追踪来自10例人类结直肠癌的150个慢病毒标记的癌细胞株系的增殖动力学变化。CNA和突变分析区分出单个克隆,同时发现在连续移植中,克隆仍具有稳定的遗传物质。尽管存在这种稳定性,但是每个克隆中慢病毒标记株系的增殖、持久生存和化疗耐受性却是可变化的。化疗会促进先前少数的或处于休眠的株系占据优势地位。总之,除了遗传多样性外,肿瘤细胞在肿瘤繁殖潜能上表现出的遗传功能差异性能够促进癌细胞的生长和治疗耐受性。

英文原稿


[Title]: Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer

   [Authors]: Antonija Kreso, Catherine A. O’Brien, Peter van Galen, Olga I. Gan, Faiyaz Notta, Andrew M. K. Brown, Karen Ng, Jing Ma, Erno Wienholds, Cyrille Dunant, Aaron Pollett, Steven Gallinger, John McPherson, Charles G. Mullighan, Darryl Shibata, and John E. Dick

[Abstract]: Intratumoral heterogeneity arises through the evolution of genetically diverse subclones during tumor progression. However, it remains unknown whether cells within single genetic clones are functionally equivalent. By combining DNA copy number alteration (CNA) profiling, sequencing, and lentiviral lineage tracking, we followed the repopulation dynamics of 150 single lentivirus-marked lineages from 10 human colorectal cancers through serial xenograft passages in mice. CNA and mutational analysis distinguished individual clones and showed that clones remained stable upon serial transplantation. Despite this stability, the proliferation, persistence, and chemotherapy tolerance of lentivirally marked lineages were variable within each clone. Chemotherapy promoted the dominance of previously minor or dormant lineages. Thus, apart from genetic diversity, tumor cells display inherent functional variability in tumor propagation potential, which contributes to both cancer growth and therapy tolerance.

原文地址

http://www.sciencemag.org/content/339/6119/543.abstract

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