Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China; Institut Curie, PSL Research University, Inserm, CNRS, Paris 75005, France.
Department of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 21198, China.
Pathol Res Pract. 2022 Aug;236:153958. doi: 10.1016/j.prp.2022.153958. Epub 2022 May 27.
Cancer metastasis accounts for the majority of cancer motility burden. For colorectal cancer (CRC), the liver is the most common site of distant metastasis. It is still little known that cancer genomic mutations, which are a cell-intrinsic and heritable property, are enriched in CRC liver metastasis. Here, we try to answer the question in the context of polyclonal seeding. In this study, we sequenced 18 pairs of colorectal cancer primary tumors and their matched liver metastasis samples. Together with public available sequencing data, we compared the mutations in 113 primary and metastasis pairs. The TP53 mutation variant allele frequency (VAF) was significantly increased in metastasis compared to the paired primary tumor, although most of the frequently observed mutations in liver metastasis foci were concordant with their matched CRC primary tumors. The results support late metastasis and polyclonal seeding. Consequently, we quantitatively compared the intratumor heterogeneity (ITH) between primary and metastasis tumors, and with the help of in silico metastasis simulation, we inferred that more than 10 cells take part in the CRC liver metastasis.
癌症转移是癌症运动负担的主要原因。对于结直肠癌（CRC），肝脏是最常见的远处转移部位。目前还不太清楚的是，癌症基因组突变是一种细胞内在的、可遗传的特性，在 CRC 肝转移中富集。在这里，我们试图在多克隆播种的背景下回答这个问题。在这项研究中，我们对 18 对结直肠癌原发肿瘤及其匹配的肝转移样本进行了测序。结合公共可用的测序数据，我们比较了 113 对原发和转移样本中的突变。与配对的原发肿瘤相比，转移中 TP53 突变的变异等位基因频率（VAF）显著增加，尽管在肝转移灶中经常观察到的大多数突变与它们匹配的 CRC 原发肿瘤一致。结果支持晚期转移和多克隆播种。因此，我们定量比较了原发肿瘤和转移肿瘤之间的肿瘤内异质性（ITH），并借助计算机模拟转移，我们推断有超过 10 个细胞参与了结直肠癌的肝转移。
