CDNA SEQUENCE AND GENOMIC STRUCTURE OF EV12B, A GENE LYING WITHIN AN INTRON OF THE NEUROFIBROMATOSIS TYPE-1 GENE

The gene responsible for neurofibromatosis type 1 (NF1), one of the more common inherited human disorders, was identified recently, and segments of it were cloned. Two translocation breakpoints that interrupt the NF1 gene in NF1 patients flank a 60-kb segment of DNA that contains the EVI2A locus (previously reported as the EVI2 locus), the human homolog of a mouse gene, Evi-2A, implicated in retrovirus-induced murine myeloid tumors. EVI2A lies within an intron of the NF1 gene and is transcribed from telomere toward centromere, opposite to the direction of transcription of the NF1 gene. Here we describe a second locus, EVI2B, also located between the two NF1 translocation breakpoints. Full-length cDNAs from the EVI2B locus detect a 2.1-kb transcript in bone marrow, peripheral blood mononuclear cells, and fibroblasts. Sequencing studies predict an EVI2B protein of 448 amino acids that is proline-rich and contains an N-terminal signal peptide, an extracellular domain with four potential glycosylation sites, a single hydrophobic transmembrane domain, and a cytoplasmic hydrophilic domain. At the level of genomic DNA the EVI2B locus lies within the same intron of the NF1 gene as EVI2A and contains a 57-bp 5′ exon that is noncoding, an 8-kb intron, and a 2078-bp 3′ exon that includes the entire open reading frame. EVI2B is transcribed in the same direction as EVI2A; its 5′ exon lies only 4 kb downstream from the 3′ exon of the EVI2A locus. In the mouse the 5′ exon of the homologous gene, Evi-2B, lies approximately 2.8 kb from the 3′ end of Evi-2A, in the midst of a cluster of viral integration sites identified in retrovirus-induced myeloid tumors; thus, Evi-2B may function as an oncogene in these tumors. © 1991.