Multi-platform genomic analysis of matched well- and dedifferentiated liposarcomas identify novel risk and progression determinants

ABSTRACT: To define mechanisms that regulate biological behavior in well- and dedifferentiated liposarcoma (WD/DDLS) subsets, we describe an integrative analysis of DNA sequence, copy number and gene expression in 9 paired WDLS and DDLS samples with validation cohorts and in vitro studies. Amplification of 12q13-15 was common to all WDLS; 6q23-25 amplifications were observed 18% of WDLS and were associated with increased TAB2 and higher local recurrence risk versus non-6q-amplified WDLS. TAB2 knockdown decreased MDM2 protein expression and induced markers of cellular senescence in 6q23-25-amplified WDLS cells but not in non-amplified WDLS of amplified DDLS cells. Amplification of 6q23-25 was not associated with DDLS recurrence risk or progression from WDLS to DDLS. Instead, pathogenic ATRX mutations, recurrent losses in 13q and gains in 8q12-21 accompanied dedifferentiation. Downregulation of the 13q-encoded genes MYCBP2 and IRS2 was observed in DDLS versus WDLS; in vitro, these genes were essential for WDLS cell differentiation. Taken together, this study defines a copy number-driven model of liposarcoma initiation, progression, and differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244163 | GEO | 2026/08/04

REPOSITORIES: GEO