Single cell DNA sequencing reveals a late-dissemination model in metastatic colorectal cancer
Menée à l'aide d'une technique de séquençage de l'ADN à l'échelle d'une seule cellule, cette étude identifie les lignées cellulaires à l'origine de la formation des métastases chez deux patients atteints d'un cancer colorectal
Metastasis is a complex biological process that has been difficult to delineate in human colorectal (CRC) cancer patients. A major obstacle in understanding metastatic lineages is the extensive intratumor heterogeneity at the primary and metastatic tumor sites. To address this problem, we developed a highly-multiplexed single cell DNA sequencing approach to trace the metastatic lineages of two CRC patients with matched liver metastases. Single cell copy number or mutational profiling was performed, in addition to bulk exome and targeted deep-sequencing. In the first patient we observed monoclonal seeding, in which a single clone evolved a large number of mutations prior to migrating to the liver to establish the metastatic tumor. In the second patient we observed polyclonal seeding, in which two independent clones seeded the metastatic liver tumor after having diverged at different time points from the primary tumor lineage. The single cell data also revealed an unexpected independent tumor lineage that did not metastasize, and early progenitor clones with the 'first hit' mutation in APC that subsequently gave rise to both the primary and metastatic tumors. Collectively, these data reveal a late-dissemination model of metastasis in two CRC patients, and provide an unprecedented view of metastasis at single cell genomic resolution.