Deletion of chromosomal region 13q14.3 in childhood acute lymphoblastic leukemia

Cavé, Hélène; Avet‐Loiseau, Hervé; Devaux, Isabelle; Rondeau, Gaelle; Boutard, Patrick; Lebrun, E.; Méchinaud, Françoise; Vilmer, E; Grandchamp, Bernard

doi:10.1038/sj.leu.2402052

Cited by 12 publications

(10 citation statements)

References 22 publications

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“…According to various authors these alterations are present in 2-38% of patients [15][16][17]. Discrepancies in findings of different authors may result from various methods employed, distinct leukemia types and differences in ethnicity of studied patients [4,5,18,19]. The percentage of cells showing deletions has not been evaluated in individual ALL patients.…”

Section: Discussionmentioning

confidence: 99%

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Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children

Studniak¹,

Maloney²,

Ociepa³

et al. 2013

pjp

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Defect in function of tumor suppressor genes may lead to initiation/progression of leukemias. RB1, CDKN2A and TP53 gene alterations are found in acute lymphoblastic leukemia (ALL) in children. Data showing a contribution of these alterations to the pathomechanism of leukemias are contradictory and their impact on a disease course still remains undefined. The main aim of the study was to identify and the characterize of RB1, CDKN2A and TP53 allele loss in ALL children patients at diagnosis. 46 children with de novo ALL were examined. Fluorescent in situ hybridization was performed on bone marrow smear preparations. We demonstrated that at least one of three investigated deletions occurred statistically more frequently in T-lineage leukemia patients (p = 0.044); this was the most frequent in respect to RB1 gene (p = 0.054). Additionally, at least one of the examined deletions was observed statistically more frequently in patients with WBC above 20 000/µl (p = 0.043), this was the most frequent for CDKN2A gene (p = 0.066). Presented results seem to give an evidence that deletions of RB1 and CDKN2A genes may contribute to the development of hyperleukocytic type of T-lineage ALL in children, nevertheless this observation needs further investigations.

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Section: Discussionmentioning

confidence: 99%

“…RB1 gene deletions as well as their possible effect on the course of a disease have been described in certain leukemias [3][4][5]. Similarly, coexistence with other high-risk markers was suggested [6,7].…”

Section: Introductionmentioning

confidence: 99%

Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children

Studniak¹,

Maloney²,

Ociepa³

et al. 2013

pjp

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“…These exons were identified using cDNA library screening (exons 1b, 3,4,[7][8][9] and RACE PCR (exons 5 and 6). The longest open reading frame of clone 1 is 297 bp,…”

Section: Discussionmentioning

confidence: 99%

“…Deletion of the long arm of chromosome 13 (13q14.3) is however the commonest, with reported frequencies of 41-51%, 1-3 but 13q being also commonly deleted in a variety of other lymphoid and myeloid malignancies. [4][5][6][7][8][9] In the majority of cases, deletion of 13q14.3 is the sole cytogenetic abnormality 10,11 and approximately 10% of CLL patients show homozygous deletion at this locus. Consequently, the existence of a tumor suppressor gene within the deleted region at 13q14.3, involved in the pathogenesis of B cell CLL, has long been postulated.…”

Section: Introductionmentioning

confidence: 99%

Deletion analysis of chromosome 13q14.3 and characterisation of an alternative splice form of LEU1 in B cell chronic lymphocytic leukemia

et al. 2002

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Heterozygous and homozygous deletions of chromosome 13q14.3 are found in 50% of patients with B cell CLL, suggesting the presence of one or more tumour suppressor genes within the deleted region. To identify candidate genes from the region, we constructed a map of 13q14.3 using a combination of genomic and cDNA library screening. The incidence of deletions in CLL patients was 51.5% encompassing a 265 kb region of minimal deletion (RMD) telomeric to markers D13S319. Two CpG islands were identified within the RMD, the telomeric of which is fully methylated whilst the more centromeric is unmethylated. A novel transcript was identified within the RMD that represents an alternative splice version of Leu1. The nine exons of this transcript span a genomic of 436 kb with exon 1 of Leu1 being the common first exon. The remaining exons were shown to be more frequently deleted than Leu1 itself. All splice forms of this transcript were detectable by RT-PCR but Leu1 detected the most abundant message on Northern blotting. Sequence analysis failed to reveal inactivating mutations in patients with heterozygous deletion of 13q14.3, although a polymorphic T to A variant was identified within exon 1 of Leu1 in leukemic and normal controls. As no mutations have been detected for Leu1 or any other transcript so far described, we cannot exclude the existence of control elements within the RMD that may regulate expression of genes lying in this region.

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“…Electrophoresis was performed on a 6% Long Ranger gel (Bioprobe, Paris, France) containing 8 M urea in a 0.6 ϫ Tris-borate-EDTA buffer. Allelic losses were scored as decreases in intensity of one allele relative to the other, as previously described (Cave et al, 2001) …”

Section: Genotypingmentioning

confidence: 99%

Molecular analysis of nonrandom 8q12 deletions in acute lymphoblastic leukemia: Identification of two candidate genes

Bardet

Couque

Cattolico

et al. 2001

Genes Chromosomes & Cancer

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Acute lymphoblastic leukemia is the most common malignancy in childhood. High-resolution allelotyping performed in our laboratory showed new chromosomal sites of nonrandom deletions. We have focused our work on 8q12 deletions, which we have found in about 4% of patients (eight of 205 informative cases). These deletions were of small size (less than 1 Mb) in all but one patient, and the deleted region common to all patients was delineated between two microsatellite markers (D8S1113 and D8S1763). This region was sequenced entirely from two overlapping bacterial artificial chromosomes. The common deleted region (120 kb) had a low GC content (37%), was composed more than 50% of LINE sequences, and contained only two candidate genes. The centromeric deletion borders were clustered within an interval of 33 kb between two microsatellite markers. This interval contains the first exon of an HMG-1-related gene (KIAA0808) and a putative gene, DL8q12, predicted to encode a protein with 231 amino acid residues with no homolog in protein databases. Analysis of the available mRNA from lymphoblastic cells of two patients with 8q12 deletions using common polymorphisms in the 3' UTR of KIAA0808 showed monoallelic expression of this gene. Identification of a biallelic polymorphism in the first exon of DL8q12 showed that this gene was deleted in two of four informative cases. Sequencing of the exons of both genes from all patients with 8q12 deletions did not show any mutation, which suggests that neither of these genes behaves as a classic tumor suppressor gene.

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Deletion of chromosomal region 13q14.3 in childhood acute lymphoblastic leukemia

Cited by 12 publications

References 22 publications

Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children

Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children

Deletion analysis of chromosome 13q14.3 and characterisation of an alternative splice form of LEU1 in B cell chronic lymphocytic leukemia

Molecular analysis of nonrandom 8q12 deletions in acute lymphoblastic leukemia: Identification of two candidate genes

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