Abstract
The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management.
Highlights
Dedifferentiated liposarcoma (DDLPS) is a rare malignant tumor with an incidence of
A total of 73.1% of the DDLPS tumors arose from the retroperitoneum or abdomen, while the distribution of the primary tumor sites varied among the three groups; tumors were most frequently located in an extremity in Japan Sarcoma Genome Consortium (JSGC)-IMSUT patients (66.7%) and in the retroperitoneum or abdomen in JSGC-NCC (78.4%) and in the Cancer Genome Atlas (TCGA) (86.0%) patients
Circos plots showed common recurrent intra- and interchromosomal rearrangements at chromosomes 1 and 12 in the DD and WD pairs (Fig. 4c; Supplementary Fig. 11a), while the heatmap of the chromosomal rearrangements revealed that the frequency of rearrangements was increased in DD compared to WD (Supplementary Fig. 11b, c). These results indicated that somatic copy-number alterations (SCNAs) and chromosomal rearrangements at chromosomes 1 and 12, but not somatic mutations, were common initial genomic events in both DD and WD and that additional copy-number alterations or chromosomal rearrangements were associated with the development of DD
Summary
Dedifferentiated liposarcoma (DDLPS) is a rare malignant tumor with an incidence of
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