title: Multifocal myxoid liposarcoma--metastasis or second primary tumor?: a molecular biological analysis.
abstract: The classification of multifocal myxoid/round cell liposarcoma, which is defined as tumor presentation in at least two separate sites before manifestation in the lungs, as either metastasis or as a second primary tumor, has essential clinical consequences. Genetically, myxoid/round cell liposarcoma is characterized by t(12;16)(q13;p11) or t(12;22)(q13;q12), and various exon fusion transcripts are described with varying incidences, which permits their use as markers for clonality. Moreover, in solid tumors, analysis of loss of heterozygozity is valuable for clonality analysis. Therefore, fifteen multifocal myxoid/round cell liposarcoma patients with two to five metachronous (n = 12) or synchronous (n = 3) localizations were investigated. Using RT-PCR, the detailed molecular characteristics of the FUS-CHOP and EWS-CHOP breakpoints were determined. Loss of heterozygozity analysis at twelve loci was then used to further analyze clonal relationships. In all patients, tumor sites showed identical FUS-CHOP fusion products. In six patients, identical rare fusion transcripts were found, supporting a clonal relationship. Nine patients had the common exon5-FUS/exon2-CHOP fusion transcript, and two of these were identified as clonally related by loss of heterozygozity analysis. In all other patients, loss of heterozygozity analysis was highly suggestive of a clonal relationship, and no evidence for interpretation of a second primary tumor was found. This study supports the metastatic nature of apparent multifocal myxoid/round cell liposarcoma.
authors.affiliation: Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. r.d.vreeze@nki.nl
authors.forename: Ronald
authors.initials: R
authors.lastname: de Vreeze
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: Petra
authors.initials: P
authors.lastname: Nederlof
authors.forename: Henrique J
authors.initials: HJ
authors.lastname: Ruijter
authors.forename: Lucie
authors.initials: L
authors.lastname: Boerrigter
authors.forename: Rick
authors.initials: R
authors.lastname: Haas
authors.forename: Frits
authors.initials: F
authors.lastname: van Coevorden
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D018208:Liposarcoma, Myxoid / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D016609:Neoplasms, Second Primary / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics; D034702:RNA-Binding Protein FUS / Q000032:analysis / Q000235:genetics; D051742:Transcription Factor CHOP / Q000032:analysis / Q000235:genetics
chemical_list: D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; C106030:TLS-CHOP fusion protein, human; D051742:Transcription Factor CHOP