The Role of RB1 and Secondary Genomic Changes in the Development of Spindle Cell and Pleomorphic Lipomas

Abstract

Spindle cell lipomas (SCL) and pleomorphic lipomas (PL) are today considered a single tumor entity (SCLPL). Atypical SCLPL, in contrast, represents a recently recognized related but distinct entity. Here we explored the correlation between genomic features and morphological aspects of SCLPL and atypical SCLPL and the role of the RB1 gene in tumor development. Seventy-one samples from 68 patients with SCLPL or atypical SCLPL, as well as a lipomatous tumor from a retinoblastoma patient with a germline pathogenic variant in the RB1 gene, and two pleomorphic liposarcomas were analyzed using chromosome banding, high-resolution genomic arrays (SNP array), whole exome sequencing (WES), and/or RNA sequencing (RNA-seq). Common for all tumors was involvement of 13q; other recurring variants were deletion of 16q, 6q, and 17p. A minimally deleted region that only contained RB1 was found on 13q. A distinction was seen between SCL on the one hand and PL and atypical SCLPL on the other; SCL had fewer copy number aberrations in general, and loss of 17p/TP53 gene or a SNV affecting TP53 was only rarely detected in SCL but seen in the vast majority of PL and atypical SCLPL tumors. Thus, at the molecular level, SCL is different from PL/atypical SCLPL. Furthermore, the finding of the same copy number changes (loss of 13q, 6q, 16q, and 17p) in some pleomorphic liposarcomas raises the possibility that a subset of SCLPL/atypical SCLPL have the potential for malignant transformation.