| Abstract: |
MITF, TFE3, TFEB, and TFEC comprise a transcription factor family (MiT) that regulates key developmental pathways in several cell lineages. Like MYC, MiT members are basic helix-loop-helix-leucine zipper transcription factors. MiT members share virtually perfect homology in their DNA binding domains and bind a common DNA motif. Translocations of TFE3 occur in specific subsets of human renal cell carcinomas and in alveolar soft part sarcomas. Although multiple translocation partners are fused to TFE3, each translocation product retains TFE3's basic helix-loop-helix leucine zipper. We have identified the genes fused by the chromosomal translocation t(6;11)(p21.1;q13), characteristic of another subset of renal neoplasms. In two primary tumors we found that Alpha, an intronless gene, rearranges with the first intron of TFEB, just upstream of TFEB's initiation ATG, preserving the entire TFEB coding sequence. Fluorescence in situ hybridization confirmed the involvement of both TFEB and Alpha in this translocation. Although the Alpha promoter drives expression of this fusion gene, the Alpha gene does not contribute to the ORF. Whereas TFE3 is typically fused to partner proteins in subsets of renal tumors, we found that wild-type, unfused TFE3 stimulates clonogenic growth in a cell-based assay, suggesting that dysregulated expression, rather than altered function of TFEB or TFE3 fusions, may confer neoplastic properties, a mechanism reminiscent of MYC activation by promoter substitution in Burkitt's lymphoma. Alpha-TFEB is thus identified as a fusion gene in a subset of pediatric renal neoplasms. |
| Keywords: |
adult; controlled study; human tissue; unclassified drug; human cell; promoter region; dna-binding proteins; case report; gene; gene expression; protein dna binding; transcription initiation; neoplasm proteins; intron; introns; transcription factor; kidney carcinoma; kidney neoplasms; transcription factors; molecular cloning; cloning, molecular; fluorescence in situ hybridization; gene rearrangement; molecular sequence data; kidney tumor; reverse transcriptase polymerase chain reaction; nucleotide sequence; fusion gene; oncogene proteins, fusion; chromosome translocation; base sequence; chromosomes, human, pair 6; translocation, genetic; binding site; dna primers; sequence homology; protein family; genetic code; chromosomes, human, pair 11; burkitt lymphoma; oncogene myc; chromosome mapping; clonogenesis; alveolar soft part sarcoma; open reading frame; basic helix-loop-helix leucine zipper transcription factors; leucine zipper protein; transcription factor tfe3; helix loop helix protein; tumor stem cell assay; helix-loop-helix motifs; transcription factor tfeb; humans; human; female; priority journal; article; alpha gene; transcription factor mitf; transcription factor tfec
|
