Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

[well-differentiated liposarcoma]

Liposarcoma is the most common soft tissue sarcoma , but little is known about the genomic basis of this disease . Given the low cell content of this tumor type , we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing . This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM 2 , a gene that has previously been found to be amplified in well-differentiated liposarcoma . Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions , some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma . We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved , putative L 1 retrotransposon element , LOC 100507498 which resides within a gene cluster (NAV 3 , SYT 1 , PAWR ) where 6 of the 11 fusion events occurred . Interestingly , a potential gene fusion was also identified in amplified DDR 2 , which is a potential therapeutic target of kinase inhibitors such as dastinib , that are not routinely used in the treatment of patients with liposarcoma . Furthermore , 7 somatic , damaging single nucleotide variants have also been identified , including D 125 N in the PTPRQ protein . In conclusion , this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM 2 and DDR 2 .

Diseases
Validation

Diseases presenting "highly focal amplifications throughout the aneuploid tumor genome" symptom

well-differentiated liposarcoma

You can validate or delete this automatically detected symptom