Minimal barriers to invasion during human colorectal tumor growth
Minimal barriers to invasion during human colorectal tumor growth
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DOI：
10.1038/s41467-020-14908-7
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发表时间：
2020-03-09
影响因子：
16.6
通讯作者：
Shibata, Darryl
中科院分区：
文献类型：
--
作者：
Ryser, Marc D.;Mallo, Diego;Shibata, Darryl
肿瘤内异质性（ITH）可以代表克隆进化，其中具有更大适应性的亚克隆赋予更多恶性表型，并且侵袭构成进化瓶颈。或者，ITH可以代表多个亚克隆入侵的分支进化。这两个模型分别预测了一个按表型排列的亚克隆层次，或多个具有共同表型的亚克隆。我们通过合并12例人结直肠肿瘤（11例癌，1例腺瘤）的祖先，地形和表型信息，通过对325个小肿瘤区域的饱和显微切割，描绘了这些侵袭模式。大多数亚克隆（29/46，60%）共享浅表和侵袭表型。在11种癌中，9种显示出多克隆侵袭的证据，并且侵袭性和转移性亚克隆沿着祖先树在早期沿着出现。在大多数这些肿瘤中的早期多克隆侵袭表明在没有晚期瓶颈的情况下具有相似恶性潜能的共进化亚克隆的扩展，并表明在结直肠癌生长期间侵袭的障碍是最小的。
Intra-tumoral heterogeneity (ITH) could represent clonal evolution where subclones with greater fitness confer more malignant phenotypes and invasion constitutes an evolutionary bottleneck. Alternatively, ITH could represent branching evolution with invasion of multiple subclones. The two models respectively predict a hierarchy of subclones arranged by phenotype, or multiple subclones with shared phenotypes. We delineate these modes of invasion by merging ancestral, topographic, and phenotypic information from 12 human colorectal tumors (11 carcinomas, 1 adenoma) obtained through saturation microdissection of 325 small tumor regions. The majority of subclones (29/46, 60%) share superficial and invasive phenotypes. Of 11 carcinomas, 9 show evidence of multiclonal invasion, and invasive and metastatic subclones arise early along the ancestral trees. Early multiclonal invasion in the majority of these tumors indicates the expansion of co-evolving subclones with similar malignant potential in absence of late bottlenecks and suggests that barriers to invasion are minimal during colorectal cancer growth.