Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.

Unlabelled: Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery.

Predicting cancer evolution for patient benefit: Renal cell carcinoma paradigm.

Evolutionary features of cancer have important clinical implications, but their evaluation in the clinic is currently limited. Here, we review current approaches to reconstruct tumour subclonal structure and discuss tumour sampling method and experimental design influence. We describe clear-cell renal cell carcinoma (ccRCC) as an exemplar for understanding and predicting cancer evolutionary dynamics.