Novel fusion gene THBS1::ERBB2 drives a subset of superficial acral fibromyxomas

Superficial acral fibromyxoma (SAFM), is a painful, solitary, slow-growing, benign soft tissue tumour of the acral regions, typically affecting the hands and feet, for which we have little understanding of the genetic drivers. As fusion genes are well-established drivers of several types of skin tumours, we collated a large, international, multi-institutional cohort of SAFM (n=66), and performed RNA pulldown transcriptome sequencing (RNAseq) to ascertain the presence of fusion genes in this tumour type. Our study identified a novel fusion gene driver, THBS1::ERBB2, in a subset of SAFM (12% cases) that was associated with aberrant HER2 expression.