Chromosomal instability shapes spatial and temporal phenotypic diversity in a malignant peripheral nerve sheath tumour

A recent study sheds light on the role of chromosomal instability in the spatial and temporal diversity of a malignant peripheral nerve sheath tumour (MPNST). The research team employed single-cell and spatial multi-omics to thoroughly examine a primary MPNST and its multifocal recurrence. By integrating the native barcoding system used to track extensive heterogeneity in copy number alterations with mutation data, they constructed an evolutionary tree for the tumour.

This tree revealed a branching structure indicative of continuous chromosomal instability. The study also demonstrated that gene dosage effects, which result from variations in copy number, significantly contribute to phenotypic diversity and increase in a linear fashion with copy number. To gain deeper insights into the interactions between tumour cells and their microenvironment, the researchers utilized spatial genomics, aided by laser capture microdissection and spatial transcriptomics, and performed in situ lineage tracing in the human tumour.

This study highlights the potential of combining bulk, single-cell, and spatial techniques to elucidate cancer evolution in both time and space, and to establish a detailed link between genotype and phenotype.