Alternative titles; symbols
HGNC Approved Gene Symbol: DLEU2
Cytogenetic location: 13q14.2 Genomic coordinates (GRCh38): 13:49,982,549-50,125,541 (from NCBI)
Loss of chromosome 13q14 is a frequent cytogenetic change in B-cell chronic lymphocytic leukemia (BCLL; see 109543), suggesting the presence of a putative tumor suppressor gene at this locus. By constructing a detailed restriction and transcriptional map of a 130-kb minimally deleted region, screening a panel of primary BCLL clones, EST database searching, and deletion mapping, Liu et al. (1997) identified 2 genes, DLEU1 (605765) and DLEU2, which they called Leu1 and Leu2, in a 10-kb minimally deleted area. The DLEU2 gene encodes a predicted 84-amino acid protein. Northern blot analysis revealed strong expression of 1.4- and 1.8-kb transcripts in thymus and testis only.
Corcoran et al. (2004) identified multiple DLEU2 transcripts produced through exon skipping, inclusion of introns, and use of alternative internal splice donor or acceptor sites. PCR analysis revealed tissue-specific expression of several DLEU2 splice variants, and most tissues expressed multiple variants. The RFP2 gene (TRIM13; 605661) overlaps DLEU2 in the antisense orientation in both mice and humans, and in situ hybridization of mouse embryos revealed coexpression of Dleu2 with Rfp2 in all tissues examined. Corcoran et al. (2004) found that RFP2 encodes a putative bicistronic transcript containing ORFs for both RFP2 and DLTET (KCNRG; 607947), as well as monocistronic transcripts. The nucleotide sequences of mouse and human DLEU2 cDNAs are highly conserved, but not the putative ORFs, suggesting that DLEU2 may be a noncoding RNA that regulates RFP2 expression.
Liu et al. (1997) determined that the DLEU2 gene lacks a TATA box, but it has several potential cis-acting DNA elements.
Corcoran et al. (2004) determined that the DLEU2 gene spans 143 kb and contains 15 exons, including 2 alternative first exons (1A and 1B). The putative bicistronic RFP2/DLTET gene is located between exons 10 and 12 of DLEU2 in the antisense orientation. All RFP2 and DLTET exons arise from DLEU2 introns except for RFP2 exon 1A, which directly overlaps DLEU2 exon 11. The intron between DLEU2 exons 1A and 1B contains the first 4 exons of DLEU1, which is transcribed in the opposite orientation to DLEU2. DLEU2 intron 6 contains 2 microRNA genes, MIRN15A (609703) and MIRN16-1 (609704).
Liu et al. (1997) mapped the DLEU2 gene to chromosome 13q14.
Corcoran et al. (2004) mapped the mouse Dleu2 gene to a region of chromosome 14 that shares homology of synteny with human chromosome 13q14.3.
Liu et al. (1997) failed to detect any intragenic or point mutations in DLEU1 and DLEU2 in 170 CLL samples. However, the first exon of each gene was deleted in all cases of 13q14 loss examined.
Corcoran, M. M., Hammarsund, M., Zhu, C., Lerner, M., Kapanadze, B., Wilson, B., Larsson, C., Forsberg, L., Ibbotson, R. E., Einhorn, S., Oscier, D. G., Grander, D., Sangfelt, O. DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouse. Genes Chromosomes Cancer 40: 285-297, 2004. [PubMed: 15188451] [Full Text: https://doi.org/10.1002/gcc.20046]
Liu, Y., Corcoran, M., Rasool, O., Ivanova, G., Ibbotson, R., Grander, D., Iyengar, A., Baranova, A., Kashuba, V., Merup, M., Wu, X., Gardiner, A., and 12 others. Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia. Oncogene 15: 2463-2473, 1997. [PubMed: 9395242] [Full Text: https://doi.org/10.1038/sj.onc.1201643]