PRAD1/lCyclin D1 proto‐oncogene: Genomic organization, 5′ dna sequence, and sequence of a tumor‐specific rearrangement breakpoint

PRAD1 (previously D11S287) is a putative proto‐oncogene at 11q13, activated by overexpression through gene rearrangement or gene amplification in several types of human tumors including parathyroid adenomas, centrocytic lymphomas and other B‐cell tumors with t(11;14), and breast cancers. PRAD1 (also CCND1) encodes cyclin D1, which may regulate the G1‐S phase transition in the cell cycle. Here, we report the cloning and characterization of the chromosomal PRAD1/cyclin D1 gene and the sequence of its promoter region. The gene spans about 15 kb and has 5 exons; its promoter region has Sp 1 binding sites and no obvious TATA box, characteristics of housekeeping genes and growth‐regulating genes. Furthermore, an E2F binding motif present close to the major transcription start site may be involved in cell cycle‐dependent expression of this gene. We also report the sequence of DNAs spanning joining regions of a reciprocal parathyroid hormone/PRAD1 gene rearrangement in a parathyroid adenoma. Comparison with normal sequences suggests that the rearrangement was not a simple break‐and‐ligate event, but rather involved multiple steps, including two microdeletions and a microinversion. Very short sequences conserved near the breakpoints and symmetrical elements in the eventually inverted DNA segment might have played a role in this illegitimate complex recombination, which may have similarities with a constitutional translocation in Duchenne muscular dystrophy. © 1993 Wiley‐Liss, Inc.

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