The der(17)t(x;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25

摘要: Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, enigmatic clinical behavior. Recent cytogenetic studies have identified a recurrent der(17) due to non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To define the interval containing Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) OATL2 (Xp11.21), cosmid from intervening genomic region. This localized breakpoint 160 kb interval. The prime candidate within previously fully sequenced region was TFE3, transcription factor gene known be fused translocation partners 1 X some papillary renal cell carcinomas. Southern blotting TFE3 probe non-germline bands several cases, consistent rearrangement possible fusion of 17q25. Amplification 5′ portion cDNAs 3′ two different novel sequence, designated ASPL, in-frame exon 4 (type fusion) or 3 2 fusion). Reverse transcriptase PCR forward primer ASPL reverse detected ASPL-TFE3 transcript all (12/12: 9 type 1, 2), establishing utility assay diagnosis ASPS. Using appropriate primers, reciprocal transcript, TFE3-ASPL, only one 12 nature most supporting as its oncogenically significant product. maps chromosome 17, ubiquitously expressed, matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. cDNA open reading frame encodes predicted protein 476 amino acids that contains carboxy-terminal UBX-like domain shows similarity proteins unknown function model organisms. replaces N-terminal by sequences, while retaining DNA-binding domain, implicating transcriptional deregulation pathogenesis tumor, biology other translocation-associated sarcomas.