A Patient with Myxoid/Round Cell Liposarcoma (MRCL) Involving the Well-known Translocation t(12;22): A Case Report with the Cytogenomic Landscape of this Rearrangement

Carlos A Tirado; Wendy Su; Vanessa Chia; Melody Zaki; Ruby Tang; Krystal Eastwood; M Teresa Guardiola; Ari Rao

A Patient with Myxoid/Round Cell Liposarcoma (MRCL) Involving the Well-known Translocation t(12;22): A Case Report with the Cytogenomic Landscape of this Rearrangement

J Assoc Genet Technol. 2022;48(2):68-75.

Authors

Carlos A Tirado^{1

2}, Wendy Su^{3

1}, Vanessa Chia^{3

1}, Melody Zaki^{3

1}, Ruby Tang^{3

1}, Krystal Eastwood², M Teresa Guardiola², Ari Rao²

Affiliations

¹ The International Circle of Genetics Studies, Los Angeles, CA.
² Baylor Scott and White Health, Department of Pathology, Temple, TX.
³ University of California Los Angeles, Los Angeles, CA.

PMID: 35660675

Abstract

Myxoid/Round Cell Liposarcoma (MRCL) is characterized as a soft tissue sarcoma that is associated with unusual patterns of metastasis to extrapulmonary sites, such as bones and other soft tissue sites. Here, we present a case of a 48-year-old male patient, diagnosed with MRCL. The patient presented with a grade 1 myxoid liposarcoma in his left leg. DNA FISH analysis showed variant rearrangements of the EWSR1 (22q12) gene and loss of the 5' DDIT3 (CHOP 12q13) gene. The variant rearrangement showed one or two fusions with multiple separated (rearranged) signals. The EWSR1-DDIT3 rearrangement has been reported in MRCL. The variant rearrangements of the EWSR1 (22q12) gene findings correlate with concurrent conventional cytogenetic findings and were described as nuc ish(EWSR1x2) (5'EWSR1 sep 3'EWSR1x1)[128/100],(5'EWSR1,3'EWSR1)x1~3(5'EWSR1 con 3'EWSR1x1~2)[57/100]. The variant rearrangements of the DDIT3 (CHOP 12q13) gene findings were described as nuc ish(5'DDIT3x1,3'DDIT3x2)(5'DDIT3 con 3'DDIT3x1)[195/200]. Molecular cytogenetic studies also showed a rearrangement of EWSR1 (22q12) in 64% of nuclei and variant rearrangement in 31.5% of nuclei. A loss of DDIT3's (12q13) 5' signal was found in 97.5% of interphase nuclei. Molecular pathology results indicated the patient was positive for EWSR1 (exon 7) and DDIT3 (exon 2) fusion. The patient underwent radiation therapy pre-resection of the myxoid liposarcoma. The most common form of MRCL is associated with t(12;16)(q13;p11), leading to FUS-CHOP and EWS-CHOP fusion proteins acting as aberrant transcription factors. The key element here is that this EWSR1-DDIT3 rearrangement led to a translocation t(12;22)(q13;q12) which is a rare cytogenetic event that led to the development of MRCL in this patient.