Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal
A partir d'échantillons de tumeurs primitives et de métastases prélevés sur des patients atteints d'un carcinome rénal à cellules claires, ces trois études mettent en évidence un ensemble d'événements génomiques permettant de décrire la trajectoire évolutionniste d'une tumeur, de sa croissance initiale jusqu'à la formation de métastases
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.