title: Molecular alterations of monophasic synovial sarcoma: loss of chromosome 3p does not alter RASSF1 and MLH1 transcriptional activity.
abstract: Differential diagnosis of monophasic synovial sarcoma requires the detection of specific biological markers. In this study we evaluated the presence of molecular alterations in 15 monophasic synovial sarcomas. Multiple changes affecting chromosome arms were detected by CGH-array in all microdissected cases available, and an association between gain or loss of specific regions harbouring cancer progression-associated genes and aneuploid status was found. The most frequent alteration was loss of 3p including 3p21.3-p23 region that, however, did not involve the promoter regions of the corresponding genes, RASSF1 and MLH1. Using Real-Time PCR, mRNA levels of both resulted moderately high compared to normal tissue; however, the weak to absent protein expression suggests RASSF1 and MLH1 post-transcription deregulation. Moreover, immunohistochemical analysis revealed that both mesenchymal and epithelial antigens were present in diploid tumours. These findings confirm the genetic complexity of monophasic synovial sarcoma and underline the need to integrate different analyses for a better knowledge of this tumour, essential to investigate new diagnostic and prognostic markers.
authors.affiliation: Laboratory of Oncologic Research, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pazzaglia
authors.forename: M S
authors.initials: MS
authors.lastname: Benassi
authors.forename: P
authors.initials: P
authors.lastname: Ragazzini
authors.forename: G
authors.initials: G
authors.lastname: Gamberi
authors.forename: F
authors.initials: F
authors.lastname: Ponticelli
authors.forename: A
authors.initials: A
authors.lastname: Chiechi
authors.forename: C M
authors.initials: CM
authors.lastname: Hattinger
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.forename: M
authors.initials: M
authors.lastname: Alberghini
authors.forename: L
authors.initials: L
authors.lastname: Zanella
authors.forename: P
authors.initials: P
authors.lastname: Picci
authors.forename: M
authors.initials: M
authors.lastname: Mercuri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D018396:Mucin-1 / Q000032:analysis / Q000235:genetics; D000070957:MutL Protein Homolog 1; D009372:Neoplasms, Connective Tissue / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D013584:Sarcoma, Synovial / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D014746:Vimentin / Q000032:analysis / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D018396:Mucin-1; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D014746:Vimentin; D007633:Keratins; D000070957:MutL Protein Homolog 1