Short telomeres on human chromosome 17p. Nat Genet 18: 76-80

Terry Fox Laboratory for Hematology/Oncology, British Columbia Cancer Research Centre, Vancouver, Canada.
Nature Genetics (Impact Factor: 29.65). 02/1998; 18(1):76-80. DOI: 10.1038/ng0198-018
Source: PubMed

ABSTRACT Human chromosomes terminate in a series of T2AG3 repeats, which, together with associated proteins, are essential for chromosome stability. In somatic cells, these sequences are known to be gradually lost through successive cells divisions; however, information about changes on specific chromosomes is not available. Individual telomeres could mediate important biological effects as was shown in yeast, in which loss of a single telomere results in cell-cycle arrest and chromosome loss. We now demonstrate by quantitative fluorescence in situ hybridization (Q-FISH; ref. 7) that the number of T2AG3 repeats on specific chromosome arms is very similar in different tissues from the same donor and varies only to some extent between donors. In all sixteen individuals studied, telomeres on chromosome 17p were shorter than the median telomere length--a finding confirmed by analysis of terminal restriction fragments from sorted chromosomes. These observations provide evidence of chromosome-specific factors regulating the number of T2AG3 repeats in individual telomeres and raise the possibility that the relatively short telomeres on chromosome 17p contribute to the frequent loss of 17p alleles in human cancers.

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Available from: Rabab K. Ward, Jan 07, 2015
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    • "Quantitation of telomere length using a telomeric peptide nucleic acid (PNA) probe was done for the first time in 1996 by Lansdorp et al. [32]. Chromosome-specific features were proposed to control telomere length because particular telomere lengths were associated with specific chromosomes [33]. Telomeres on specific chromosome arms were also found to have interallelic differences, through the use of STELA, a polymerase chain reaction–based technique [34] [35]. "
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    ABSTRACT: Mouse plasmacytoma (PCT) can develop within 45 days when induced by a v-abl/myc replication-deficient retrovirus. This fast-onset PCT development is always associated with trisomy of cytoband E2 of mouse chromosome 11 (11E2). Trisomy of 11E2 was identified as the sole aberration in all fast-onset mouse PCTs in [T38HxBALB/c]N congenic mice, with a reciprocal translocation between chromosome X and 11 (rcpT(X;11)) (Genes Cancer 2010;1:847-858). Using this mouse model, we have now examined the overall and individual telomere lengths in fast-onset PCTs compared with normal B cells using two-dimensional and three-dimensional quantitative fluorescent in situ hybridization of telomeres. We found fast-onset PCTs to have a significantly different three-dimensional telomere profile, compared with primary B cells of wild-type littermates with and without rcpT(X;11) (P < .0001 and P = .006, respectively). Our data also indicate for primary PCT cells, from the above mouse strain, that the translocation chromosome carrying 11E2 is the only chromosome with telomere lengthening (P = 4 x 10(-16)). This trend is not seen for T(X;11) in primary B cells of control [T38HxBALB/c]N mice with the rcpT(X;11). This finding supports the concept of individual telomere lengthening of chromosomes that are functionally important for the tumorigenic process.
    Neoplasia (New York, N.Y.) 04/2012; 14(4):344-51. DOI:10.1593/neo.12446 · 5.40 Impact Factor
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    • "The shortest telomere 17p in the healthy population was previously suggested to be associated with human cancers, because the p53 gene and other potential tumor-suppressor genes are located on 17p [20] [38]. Figure 4. Dot plots for z value analysis of " acquired " long RTLs. "
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    ABSTRACT: Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found that telomeres at some specific chromosome arms remain well maintained or even lengthened in a high frequency (27/32) of leukemia cases. In particular, 10 chromosome arms, 4q, 5p, 7q, 11p, 13p, 13q, 14p, 15p, 18p, and Xp, with long telomeres were consistently identified in different samples, and six of them (4q, 5p, 13p, 13q, 14p, and Xp) with relatively long telomeres were also observed in normal samples, but they appeared in lower occurrence rate and shorter RTL than in CML samples. Our results strongly indicate the presence of a special leukemia cell population, or a clone, originated from a common progenitor that is characterized with chromosome arm-specific long telomeres. We suggest that relatively long telomeres located at key chromosomes could be preferentially maintained or further elongated during the early stage of malignant transformation.
    Neoplasia (New York, N.Y.) 06/2011; 13(6):550-60. DOI:10.1593/neo.11358 · 5.40 Impact Factor
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    • "These two techniques provide a global picture of telomere lengths at the genomic and cellular levels by assessing their average length. The advent of telomere length measurement by quantitative FISH (Q-FISH) [16] has allowed a better understanding of telomere length at the chromosomal level. Besides the t(9;22)(q34;q11.2) translocation, other chromosomal aberrations have been reported during the progression of CML [17], and the critical shortening of telomeres may be related to these chromosomal changes. "
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    ABSTRACT: Chronic myeloid leukemia (CML) is a neoplasia characterized by proliferation of a myeloid cell lineage and chromosome translocation t(9;22) (q34;q11.2). As in the case of most cancers, the average telomere length in CML cells is shorter than that in normal blood cells. However, there are currently no data available concerning specific individual telomere length in CML. Here, we studied telomere length on each chromosome arm of CML cells. In situ hybridization with peptide nucleic acid probes was performed on CML cells in metaphase. The fluorescence intensity of each specific telomere was converted into kilobases according to the telomere restriction fragment results for each sample. We found differences in telomere length between short arm ends and long arm ends. We observed recurrent telomere length changes as well as telomere length maintenance and elongation in some individual telomeres. We propose a possible involvement of individual telomere length changes to some chromosomal abnormalities in CML. We suggest that individual telomere length maintenance is chromosome arm-specific associated with leukemia cells.
    Neoplasia (New York, N.Y.) 11/2009; 11(11):1146-54. DOI:10.1593/neo.09836 · 5.40 Impact Factor
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