Comparative Sequence Analysis of a Region on Human Chromosome 13q14, Frequently Deleted in B-Cell Chronic Lymphocytic Leukemia, and Its Homologous Region on Mouse Chromosome 14

Kapanadze, Bagrat; Makeeva, Natalia; Corcoran, Martin; Jareborg, Niclas; Hammarsund, Marianne; Baranova, Ancha; Zabarovsky, Eugene R.; Vorontsova, Olga; Merup, Mats; Gahrton, Gösta; Jansson, Monika; Yankovsky, N. K.; Einhorn, Stefan; Oscier, David; Grander, T. Dan; Sangfelt, Olle

doi:10.1006/geno.2000.6386

Cited by 24 publications

(19 citation statements)

References 29 publications

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“…This analysis reliably identified only 2 of 171 CLL cases with deletions shorter than del13q14 type Ia lesions, implying that removal of f0.8 Mb of chromosomal material from f49.5 to f50.5 Mb is required for the biology of del13q14 type Ia lesions (10,12,15,16,18,19,36).…”

Section: Resultsmentioning

confidence: 95%

“…Efforts by multiple groups have identified candidate genes within an f1 Mb stretch on chromosome 13 that have each been implicated in CLL del13q14 biology; nonetheless, mutations in these genes have not been identified and questions remain as to the validity of reducing the biology of del13q14 to a minimal deleted region or a single-gene mutation/expression event (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Analysis of del13q14 is further complicated by an evolving understanding of resident gene structure and the discovery of complex noncoding RNAs (20).…”

Section: Introductionmentioning

confidence: 99%

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Integrated Genomic Profiling of Chronic Lymphocytic Leukemia Identifies Subtypes of Deletion 13q14

et al. 2008

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Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness with a variable clinical course. Loss of chromosomal material on chromosome 13 at cytoband 13q14 is the most frequent genetic abnormality in CLL, but the molecular aberrations underlying del13q14 in CLL remain incompletely characterized. We analyzed 171 CLL cases for loss of heterozygosity and subchromosomal copy loss on chromosome 13 in DNA from fluorescence-activated cell sorting-sorted CD19 + cells and paired buccal cells using the Affymetrix XbaI 50k SNP array platform. The resulting highresolution genomic maps, together with array-based measurements of expression levels of RNA in CLL cases with and without del13q14 and quantitative PCR-based expression analysis of selected genes, support the following conclusions: (a) del13q14 is heterogeneous and composed of multiple subtypes, with deletion of Rb or the miR15a/miR16 loci serving as anatomic landmarks, respectively; (b) del13q14 type Ia deletions are relatively uniform in length and extend from breakpoints close to the miR15a/miR16 cluster to a newly identified telomeric breakpoint cluster at the f50.2 to 50.5 Mb physical position; (c) LATS2 RNA levels are f2.6-fold to 2.8-fold lower in cases with del13q14 type I that do not delete Rb, as opposed to del13q14 type II or all other CLL cases; (d) PHLPP RNA is absent in f50% of CLL cases with del13q14; and (e) f15% of CLL cases display marked reductions in miR15a/miR16 expression that are often but not invariably associated with bi-allelic miR15a/miR16 loss. These data should aid future investigations into biological differences imparted on CLL by different del13q14 subtypes.

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Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Integrated Genomic Profiling of Chronic Lymphocytic Leukemia Identifies Subtypes of Deletion 13q14

et al. 2008

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“…28 Two genes in this region have been shown to be highly conserved between mouse and humans, DLEU2 and RFP2 (also called LEU5). 29 Despite the linkage to this particular region of DNA in CLL, no somatic mutations in this region have been detected in CLL patients, 30 and none were found in the NZB strain of mouse (data not shown). In addition to the presence of DLEU2 and RFP2 in the human 13q14 and the region of synteny in the mouse chromosome 14, there are 2 microRNAs genes found in the intronic region of DLEU2 in both murine and human, mir-15a and mir-16-1.…”

Section: Linkage Analysis Of Murine Model Of Human B-cll 5083mentioning

confidence: 89%

Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice

Raveché¹,

Salerno²,

Scaglione³

et al. 2007

Blood

266

219

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“…As a means of defining the important transcriptional units in the region, we previously compared the human genomic sequence with that of a limited 18-kb mouse sequence from the syntenic region in order to determine which transcripts are highly conserved. These studies showed that the DLEU1 gene was not conserved at the nucleotide sequence level, which would be expected in key genes such as tumor suppressors or oncogenes (Kapanadze et al, 2000). In contrast, the DLEU2 and RFP2/LEU5 genes were found to be conserved at the genomic sequence level between human and mouse.…”

Section: Introductionmentioning

confidence: 93%

DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouse

Corcoran

Hammarsund²,

Zhu³

et al. 2004

Genes Chromosomes & Cancer

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Our group previously identified two novel genes, RFP2/LEU5 and DLEU2, within a 13q14.3 genomic region of loss seen in various malignancies. However, no specific inactivating mutations were found in these or other genes in the vicinity of the deletion, suggesting that a nonclassical tumor-suppressor mechanism may be involved. Here, we present data showing that the DLEU2 gene encodes a putative noncoding antisense RNA, with one exon directly overlapping the first exon of the RFP2/LEU5 gene in the opposite orientation. In addition, the RFP2/LEU5 transcript can be alternatively spliced to produce either several monocistronic transcripts or a putative bicistronic transcript encoding two separate open-reading frames, adding to the complexity of the locus. The finding that these gene structures are conserved in the mouse, including the putative bicistronic RFP2/LEU5 transcript as well as the antisense relationship with DLEU2, further underlines the significance of this unusual organization and suggests a biological function for DLEU2 in the regulation of RFP2/LEU5.

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Comparative Sequence Analysis of a Region on Human Chromosome 13q14, Frequently Deleted in B-Cell Chronic Lymphocytic Leukemia, and Its Homologous Region on Mouse Chromosome 14

Cited by 24 publications

References 29 publications

Integrated Genomic Profiling of Chronic Lymphocytic Leukemia Identifies Subtypes of Deletion 13q14

Integrated Genomic Profiling of Chronic Lymphocytic Leukemia Identifies Subtypes of Deletion 13q14

Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice

DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouse

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