Role for CCG-trinucleotide repeats in the pathogenesis of chronic lymphocytic leukemia

Auer, Rebecca; Jones, Christopher T.; Müllenbach, Roman; Syndercombe‐Court, Denise; Milligan, Donald; Fegan, Christopher; Cotter, Finbarr E.

doi:10.1182/blood.v97.2.509

Cited by 36 publications

(34 citation statements)

References 57 publications

(80 reference statements)

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“…21 Other groups have reported data suggesting that there is a slightly more telomeric but overlapping region that does not include ATM. [21][22][23] This finding was corroborated by Lehmann et al 5 who also observed a second commonly deleted region at 11q that is telomeric to the ATM gene when they used SNP arrays to karyotype CLL samples. It is postulated that this region may harbor another TSG associated with the development of CLL, and that concurrent deletion of ATM and this other TSG may contribute to a poor prognosis.…”

mentioning

confidence: 55%

The rewards and challenges of array-based karyotyping for clinical oncology applications

Hagenkord

Chang

2009

Leukemia

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mentioning

confidence: 55%

The rewards and challenges of array-based karyotyping for clinical oncology applications

Hagenkord

Chang

2009

Leukemia

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“…These sites (Fig. 5, pink arrows) were located nonrandomly within the sites of tumor-associated deletions (P ϭ 0.95; see Methods) and in the vicinity of CBRs but not precisely at the breakpoints similarly to fragile sites, where the breaks occur not necessarily very close to repeat (8). Moreover the repeat numbers 2, 3, and 8, identified with the highest scores, were located in two of our CERs (CER1 and CER2) and close to the overlapping region of three homozygous deletions in HD4.…”

Section: Tumor-associated Deletions On 3p Colocalize With Evolutionarilymentioning

confidence: 97%

“…Such regions may harbor multiple tumor-suppressor gene candidates (2,6). High frequency of chromosome rearrangements, the occurrence of multiple deletion breakpoints within small segments (deletion ''hot spots'') (4,5), and changes affecting groups of genes suggested that yet-unknown unstable sites may play an important role in tumor-associated chromosome instability as it was demonstrated for known fragile sites, virus integration sites, and pericentromeric regions (7)(8)(9)(10). Genetic instability may participate in evolutionary genome rearrangements as shown for pericentromeric chromosomal regions (11), and it has been suggested that the hot spots of tumor-related deletions on 3p may coincide with the evolutionary chromosome breakpoints (1).…”

mentioning

confidence: 99%

Coincidence of synteny breakpoints with malignancy-related deletions on human chromosome 3

Kost‐Alimova¹,

Kiss²,

Fedorova³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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We have found previously that during tumor growth intact human chromosome 3 transferred into tumor cells regularly looses certain 3p regions, among them the Ϸ1.4-Mb common eliminated region 1 (CER1) at 3p21.3. Fluorescence in situ hybridization analysis of 12 mouse orthologous loci revealed that CER1 splits into two segments in mouse and therefore contains a murine͞human conservation breakpoint region (CBR). Several breaks occurred in tumors within the region surrounding the CBR, and this sequence has features that characterize unstable chromosomal regions: deletions in yeast artificial chromosome clones, late replication, gene and segment duplications, and pseudogene insertions. Sequence analysis of the entire 3p12-22 revealed that other cancer-associated deletions (regions eliminated from monochromosomal hybrids carrying an intact chromosome 3 during tumor growth and homozygous deletions found in human tumors) colocalized nonrandomly with murine͞human CBRs and were characterized by an increased number of local gene duplications and murine͞human conservation mismatches (single genes that do not match into the conserved chromosomal segment). The CBR within CER1 contains a simple tandem TATAGA repeat capable of forming a 40-bp-long secondary hairpin-like structure. This repeat is nonrandomly localized within the other tumor-associated deletions and in the vicinity of 3p12-22 CBRs.

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“…Physical maps of the 13q14 and 11q22-23 larger commonly deleted regions, encompassing the critical minimal-deleted regions (MinDRs), were compiled from a combination of updated database of the human genome sequence (http:// www.ncbi.nlm.nih.gov/mapview), previous publications defining the deleted regions (Auer et al, 2001, Stilgenbauer et al, 1996Zhu et al, 1999;Kitamura et al, 2000;Bullrich et al, 2001;Mabuchi et al, 2001;Migliazza et al, 2001;Wolf et al, 2001) and our own 40 Mb 11q21-qter YAC/bacterial artificial chromosome and P1 artificial chromosome contig map (Tunnacliffe et al, 1999).…”

Section: Identification Of the Human 13q14 And 11q22-23 Commonly Delementioning

confidence: 99%

“…The region of deletion at 11q22-23 is much larger and less well defined. A 2-3 Mb region has been reported and is covered by three yeast artificial chromosome (YAC) clones y801e11, y975h6 and y755b11 containing the ATM gene (Stilgenbauer et al, 1996), although work from two other groups suggests a slightly more telomeric but overlapping region (Zhu et al, 1999;Auer et al, 2001).…”

mentioning

confidence: 99%

The 13q and 11q B‐cell chronic lymphocytic leukaemia‐associated regions derive from a common ancestral region in the zebrafish

2007

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SummaryLoss of the long arm of chromosomes 11 and 13 is the most consistent cytogenetic abnormalities for patients with B‐cell chronic lymphocytic leukaemia (B‐CLL). They suggest the presence of as yet unidentified tumour suppressor genes within well‐defined minimal‐deleted regions (MinDRs). We have identified 38 orthologues of the human genes in MinDRs in zebrafish cDNA and syntenic regions for the human deletions in the zebrafish genome. One region on chromosome 9 in the zebrafish genome is of potential interest. Within chromosome 9, five genes and two microRNAs were identified with shared synteny to the MinDRs in B‐CLL (two genes to human chromosome 11, three to human chromosome 13 and two chromosome 13 microRNAs). The critical region on zebrafish chromosome 9 maps to the MinDR for both human chromosomes, suggesting a common ancestry for B‐CLL tumour suppressor genes. Target‐selected mutagenesis to identify zebrafish mutants with knock‐outs of genes in this region will allow analysis of their in vivo potential for lymphoproliferation and may define causative genes for B‐CLL within human chromosomes 11q and 13q. Our study provides an explanation for involvement of both 11q and 13q in B‐CLL and the potential to develop animal models for this common lymphoproliferative disorder.

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Role for CCG-trinucleotide repeats in the pathogenesis of chronic lymphocytic leukemia

Cited by 36 publications

References 57 publications

The rewards and challenges of array-based karyotyping for clinical oncology applications

The rewards and challenges of array-based karyotyping for clinical oncology applications

Coincidence of synteny breakpoints with malignancy-related deletions on human chromosome 3

The 13q and 11q B‐cell chronic lymphocytic leukaemia‐associated regions derive from a common ancestral region in the zebrafish

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