Translocation t(12;16)(q13;pll) in Myxoid Liposarcoma of a Child and Implica of the Human int‐1 Gene in Tumorigenesis

Abstract

Cytogenetic and gene analyses were performed in a child with myxoid liposarcoma (MLS). A reciprocal chromosome translocation t(12;16)(q13:pll) was found in the tumor cells. This result, combined with the previous reports of a similar translocation in adult MLS strongly suggests that this translocation may be a characteristic cytogenetic marker in MLS. The human int‐1 gene has been reported to be located close to the 12q1 breakpoint associated with MLS. Therefore, we examined the rearrangement of the human int‐1 gene by Southern blotting analysis. When genomic DNAs from the tumor cells were digested with KpnI, EcoRI and BamHI, no difference was seen compared to peripheral blood leukocytes (PBL) DNAs from a normal individual. However, with HindIII digestion there appeared a 3.1 kb fragment in tumor cell DNA as compared to a 2.8 kb fragment in DNAs prepared from normal PBL and the patient's PBL. These findings suggest that the int‐1 gene may be implicated in tnmorigenesis of MLS with t(12;16)(q13;pll).

Pediatric liposarcoma: A case series and literature review

“…While data in pediatrics remain sparse regarding recurring genomic alterations, specific cytogenetic and molecular testing should be performed for LPS subtypes with characteristic findings to aid in diagnosis, and broader molecular testing should be strongly considered in those with PLPS, MPLPS, or those with advanced disease as they may harbor potentially actionable alterations. The pathognomonic MLPS translocations FUS‐DDIT3 ( FUS‐CHOP ) or CHOP‐EWS 16,17,58 were present in four of seven tumors in our institutional series, and in 79% of cases with reported molecular testing in the literature 6,20,23,44 . Trabectedin has been shown to displace the FUS‐CHOP protein from gene promoters, leading to adipocytic differentiation of MLPS 59 and decreases the risk of disease progression in adult patients with liposarcoma 60 .…”

“…Forty articles describing 261 patients met inclusion criteria 6,15,20–57 . Data from the literature were combined with the TCH cohort for the analysis (Table 2).…”

“…The pathognomonic MLPS translocations FUS-DDIT3 (FUS-CHOP) or CHOP-EWS 16,17,58 were present in four of seven tumors in our institutional series, and in 79% of cases with reported molecular testing in the literature. 6,20,23,44 Trabectedin has been shown to displace the FUS-CHOP protein from gene promoters, leading to adipocytic differentiation of MLPS 59 and decreases the risk of disease progression in adult patients with liposarcoma. 60 Amplification of MDM2 and CDK4 in WDLPS and DDLPS has been reported extensively in the adult literature 9,[61][62][63][64] and was present in eight pediatric cases.…”

Histology driven systemic therapy of liposarcoma—ready for prime time?

“…MLPS usually carries a translocation of t(12;16)(q13;p11) involving the DDIT3 and FUS genes (11). A fusion of EWSR1-DDIT3 has been described less commonly.…”