Connective Tissue Oncology Society

2001 CTOS Annual Meeting Posters— Medical Oncology

NOVEL TYPE OF EWS-CHOP FUSION GENE IN TWO CASES OF LIPOSARCOMAS WITH AGGRESSIVE CLINICAL FEATURES AND ATYPICAL HISTOPATHOLOGICAL FINDINGS.
Tomitaka Nakayama¹, Taisuke Hosaka², Yasuaki Nakashima³, Katsuyuki Kusuzaki⁴, Takeharu Nakamata², Tomoki Aoyama², Takeshi Okamoto², koichi Nishijo², Takashi Nakamura¹, junya Toguchida²
¹Department of Orthopaedic Surgery Kyoto University, ²UniversityInstitiute for Frontier Medical Science Kyoto Univeresity , ³Department of Pathology Kyoto University, ⁴Department of Orthopaedic Surgery Kyoto Prof.Univ.of Med.

OBJECTIVE: Chimeric proteins consisting of TLS and CHOP or EWS and CHOP are characteristic markers for myxoid liposarcomas (MLS). At least nine different structure of TLS-CHOP fusion transcripts due to different breakpoints or alternative splicing were reported, whereas only one type consisting of exon 1to 7 of EWS and exon 2 to 4 of CHOP gene was so far reported in the case of EWS-CHOP fusion gene. Here we described our analyses of 21 MLS cases, and found a novel type of EWS-CHOP fusion gene in two cases with unique clinical and histopathological findings.

METHODS: RNAs and DNAs were extracted from surgically resected tumor tissues of 21 MLSs. RNAs with appropriate quality were available in 18 cases, and cDNAs were synthesized from them. Using these cDNAs as a template, either TLS or EWS-specific primer was used in combination of the CHOP primer to amplify TLS-CHOP or EWS-CHOP fusion genes, respectively. Amplified fragments were directly sequenced to determine the structure of fusion genes. In the remaining three cases, genomic long-distance PCR was performed to amplify genomic fragments encompassing the genomic fusion points.

RESULTS: By the combination of RT-PCR and genomic long-distance PCR analysis, we found either TLS-CHOP or EWS-CHOP fusion genes in all of 21 cases. Among them, 17 cases (81%) were found to have TLS-CHOP fusion genes. The structure of these fusion genes were type 1 in five cases, type 2 in eight, type 3 in one, type 4 in two and type 5 in one case according to the classification of previous reports including ours. EWS-CHOP fusion genes were detected in four cases (19%), of which two were found to consist of exon 1 to 7 of EWS and exon 2 to 4 of CHOP, This structure is identical with those of five cases with EWS-CHOP fusion genes in previous literatures. The structure of the other two cases was found to be a novel one, consisting of exon 1 to 10 of EWS and exon 2 to 4 of CHOP gene. The clinical and pathological findings of these two cases with this novel EWS-CHOP fusion gene were quite remarkable in contrast with other cases. Both presented a rapid growing huge mass, showing good response to preoperative chemotherapy, but developing local recurrece within 12 months. Tumor tissues showed monotonous proliferation of small cells with minimum adipocytic features in abundant myxoid matrix and few vascular structures. These features were not compatible with classic myxoid or round cell liposaroma, and also clearly different from pleomorphic or well-differentiated liposarcoma.

CONCLUSION: The fact that clinical and histopathological findings of two cases with a novel EWS-CHOP gene shared several unique features suggest the unique property of this type of rare fusion gene, which may be related to develop a distinct type of liposarcomas.