Clone Phylogenetics Reveals Metastatic Tumor Migrations, Maps, and Models.
Clone Phylogenetics Reveals Metastatic Tumor Migrations, Maps, and Models.
复制标题
DOI：
10.3390/cancers14174326
复制
发表时间：
2022-09-04
期刊：
影响因子：
5.2
通讯作者：
Kumar, Sudhir
中科院分区：
文献类型：
--
作者：
Chroni, Antonia;Miura, Sayaka;Hamilton, Lauren;Vu, Tracy;Gaffney, Stephen G.;Aly, Vivian;Karim, Sajjad;Sanderford, Maxwell;Townsend, Jeffrey P.;Kumar, Sudhir
转移是指癌细胞在器官间扩散，是癌症死亡的主要原因。对肿瘤测序数据的分析为重建转移细胞迁移的路径提供了一种手段。我们的重建显示，许多转移瘤很可能来自原发瘤的原有转移。此外，肿瘤部位之间的多克隆交换也很常见。总而言之，癌细胞的迁移模式往往很复杂，而且在不同患者之间差异很大。转移细胞的扩散路径在医学上是检测不到的，甚至看不见。肿瘤变异的分子进化分析提供了一种回溯性推断转移转移历史的方法，并回答了诸如大多数转移是来自原发肿瘤内克隆还是来自已有转移内克隆的问题，以及转移的演化是否与任何提出的模型大体一致。我们通过系统的以患者为中心的回顾分析来寻求这些基本问题的答案，该分析绘制了许多癌症中肿瘤细胞迁移的动态演化史。我们分析了51名癌症患者的肿瘤遗传异质性，发现大多数转移移行史最好地用转移肿瘤进化的混合模型来描述。综合转移转移病史，我们发现新的肿瘤播种来自先前存在的转移的克隆，就像它们来自原发肿瘤的克隆一样多。在来源和受体肿瘤之间也有许多克隆交换。因此，对肿瘤变异的分子系统学分析提供了一种对癌症患者转移移行史的一般模式的回顾。
Metastasis is the spread of cancer cells across organs and is a major cause of cancer mortality. Analysis of tumor sequencing data provides a means toward the reconstruction of routes of metastatic cell migrations. Our reconstructions demonstrated that many metastases were likely seeded from pre-existing metastasis of primary tumors. Additionally, multiple clone exchanges between tumor sites were common. In conclusion, the pattern of cancer cell migrations is often complex and is highly variable among patients. Dispersal routes of metastatic cells are not medically detected or even visible. A molecular evolutionary analysis of tumor variation provides a way to retrospectively infer metastatic migration histories and answer questions such as whether the majority of metastases are seeded from clones within primary tumors or seeded from clones within pre-existing metastases, as well as whether the evolution of metastases is generally consistent with any proposed models. We seek answers to these fundamental questions through a systematic patient-centric retrospective analysis that maps the dynamic evolutionary history of tumor cell migrations in many cancers. We analyzed tumor genetic heterogeneity in 51 cancer patients and found that most metastatic migration histories were best described by a hybrid of models of metastatic tumor evolution. Synthesizing across metastatic migration histories, we found new tumor seedings arising from clones of pre-existing metastases as often as they arose from clones from primary tumors. There were also many clone exchanges between the source and recipient tumors. Therefore, a molecular phylogenetic analysis of tumor variation provides a retrospective glimpse into general patterns of metastatic migration histories in cancer patients.
登录
查看更多内容
影响因子：
16.6
作者：
Ryser, Marc D.;Mallo, Diego;Shibata, Darryl
通讯作者：
Shibata, Darryl
影响因子：
9.7
作者：
Fisk, J. Nicholas;Mahal, Amandeep R.;Townsend, Jeffrey P.
通讯作者：
Townsend, Jeffrey P.
影响因子：
5.2
作者：
Chroni, Antonia;Vu, Tracy;Kumar, Sudhir
通讯作者：
Kumar, Sudhir
影响因子：
4.6
作者：
Miura, Sayaka;Vu, Tracy;Kumar, Sudhir
通讯作者：
Kumar, Sudhir
影响因子：
10.7
作者：
Somarelli, Jason A.;Gardner, Heather;Townsend, Jeffrey P.
通讯作者：
Townsend, Jeffrey P.