Interstitial telomeric sequences at the junction site of a jumping translocation

Vermeesch, Joris Robert; Petit, P; Speleman, Franki; Devriendt, Koen; Fryns, Jean‐Pierre; Marynen, Peter

doi:10.1007/s004390050440

Cited by 58 publications

(47 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies using random integration of a 1.6-kb telomere sequence failed to detect repeat-induced instability by less sensitive cytogenetic methods (20). Thus, these studies define the telomere repeat sequence as a destabilizing element in the interior of a mammalian chromosome, providing direct support for previous correlations between interstitial telomere repeats and chromosome rearrangements (10,12,16,17,36,50,54,66,72).…”

Section: Discussionsupporting

confidence: 70%

“…The extraordinarily high instability (several percent) correlated with some naturally occurring interstitial telomere sequences (10,12,16,17,36,50,54,66,72) suggests that instability increases with telomere sequence length or with some undefined aspect of the arrangement or structure of the repeats. The approaches described here provide a means to quantify these undefined elements of telomere sequence-induced instability.…”

Section: Discussionmentioning

confidence: 99%

“…Like repeats at telomeres, interstitial repeats also appear to influence aspects of DNA metabolism in their vicinity. Cytogenetic studies in mitotically dividing cells have linked interstitial telomere repeats with sites of spontaneous and radiation-induced chromosome rearrangements (10,17,54,66), chromosome fragility (12,50), and unstable rearrangements known as jumping translocations (16,36,72). In meiotic cells in the Armenian hamster, an interstitial telomere repeat was a site of frequent chiasma formation, consistent with a hotspot for homologous recombination (4).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability

Kilburn

Shea

Sargent³

et al. 2001

Molecular and Cellular Biology

View full text Add to dashboard Cite

Telomere repeat sequences cap the ends of eucaryotic chromosomes and help stabilize them. At interstitial sites, however, they may destabilize chromosomes, as suggested by cytogenetic studies in mammalian cells that correlate interstitial telomere sequence with sites of spontaneous and radiation-induced chromosome rearrangements. In no instance is the length, purity, or orientation of the telomere repeats at these potentially destabilizing interstitial sites known. To determine the effects of a defined interstitial telomere sequence on chromosome instability, as well as other aspects of DNA metabolism, we deposited 800 bp of the functional vertebrate telomere repeat, TTAGGG, in two orientations in the second intron of the adenosine phosphoribosyltransferase (APRT) gene in Chinese hamster ovary cells. In one orientation, the deposited telomere sequence did not interfere with expression of the APRT gene, whereas in the other it reduced mRNA levels slightly. The telomere sequence did not induce chromosome truncation and the seeding of a new telomere at a frequency above the limits of detection. Similarly, the telomere sequence did not alter the rate or distribution of homologous recombination events. The interstitial telomere repeat sequence in both orientations, however, dramatically increased gene rearrangements some 30-fold. Analysis of individual rearrangements confirmed the involvement of the telomere sequence. These studies define the telomere repeat sequence as a destabilizing element in the interior of chromosomes in mammalian cells.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability

Kilburn

Shea

Sargent³

et al. 2001

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…54 We also found a stable, complex rearrangement -a four-way translocation and inversion -in a pre-B ALL cell line (REH) dedicated to non-reciprocal fusion of TEL with AML1, 55 supporting the inference that complex changes in HDLM cells, eg, the putative five-way t(8;2;13;22;14) might also be facilitatory. Several reports link JT with interstitial telomere sequences, 56,57 whether random as suggested by Andreasson et al 58 or facilitatory as implied by the current report. Both (p/q) interstitial telomeres of chr.…”

Section: Instabilitysupporting

confidence: 52%

Karyotypic dissection of Hodgkin's disease cell lines reveals ectopic subtelomeres and ribosomal DNA at sites of multiple jumping translocations and genomic amplification

MacLeod

Spitzer

Bar‐Am³

et al. 2000

Leukemia

View full text Add to dashboard Cite

Although the neoplastic significance of the chromosome changes widespread in Hodgkin's disease (HD) remains obscure, a distinct cytogenetic picture has emerged combining aneuploidy with structural rearrangements clustered at certain breakpoints. Notably absent are the recurrent chromosome translocations which distinguish other hematopoietic neoplasms and serve as clues to underlying oncogene alterations. The paucity of neoplastic cells in HD biopsies hinders detailed chromosome analysis. As an alternative, we investigated a panel of well characterized cell lines by classical and molecular cytogenetics, using single-gene and subtelomeric probes, including three autologous HD examples (HDLM-1/2/3) analyzed by 'spectral karyotyping' -the first complete HD karyotype to be documented. Although complex, most rearrangements in HDLM cells arose in vivo and included few rare but many typical HD breakpoints, notably at the r(ibosomal)DNA regions. Two types of genomic rearrangement involving DNA repeats were conspicuous: insertion and genomic amplification/coamplification of rDNA -the first genomic rDNA rearrangements to be reported in a tumor cell, and the first example of multiple 'jumping translocations' (JT). Of four subtelomeric microsatellite repeats tested in HDLM cells, three exhibited interstitial sites at JT, of which two (at 5qter and 9pter) were respectively associated with deletion of the 5q31-32 myeloid region, and coamplification of a recently described HD-recurrent amplicon at 9p2 together with transcriptionally silent rDNA. Altogether, three out of four HD cell lines carried interstitial 9p subtelomeres and rDNA rearrangements. Taken together, these data suggest tumorigenic rearrangements may be facilitated by 'hitchhiking' along with mobile DNA repeat sequences which may target gene rearrangement at 9p in HD. Southern analysis of parallel rearrangements within rDNA intergenic spacers in HDLM cells highlighted several at, or near, retroposons. As well as validating HD cell lines as cytogenetic models, and resources for identifying genes rearranged in HD, our findings warrant further investigation of the roles of DNA repeat sequences, notably subtelomeric microsatellites, rDNA spacer sequences and retroposons as facilitators and markers of tumor-gene rearrangement.

show abstract

“…[31][32][33][34] JT in such cases are, however, also cytogenetically different compared to hematologic malignancies -they preferentially involve other donor chromosome regions and are not trisomic for the jumping region. [31][32][33][34][35] Altogether, the widespread temporally heterogeneous breakpoints of the donor chromosome and the subtelomeric breakpoints on the recipient chromosomes indicate a complex origin of JT: the multiple clones most likely arose more or less simultaneously, followed by clonal selection. In this context, it is noteworthy that a small clone with +3 preceded the unbalanced JT.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of jumping translocations reveals spatial and temporal breakpoint heterogeneity

et al. 1998

View full text Add to dashboard Cite

Jumping translocations (JT) are characterized by the relocalization of the same part of a donor to several recipient chromosomes. Although JT occasionally are constitutional, most are associated with hematologic malignancies. In such cases, JT usually arise during disease progression and are associated with poor prognosis. Despite its clinical importance, this cytogenetic phenomenon has not been characterized at the molecular level. We have analyzed JT in a juvenile chronic myelomonocytic leukemia that subsequently transformed to an acute myeloid leukemia. Detailed fluorescence in situ hybridization (FISH) analyses showed that the cytogenetically identical donor breakpoint at 3q21 was highly heterogeneous. In fact, more than 10 distinct breakpoints, four of which mapped within YACs, were identified. Analyses of samples during disease progression showed that the breakpoint complexity decreased, indicating clonal selection. Hence, the 3q21 breakpoints displayed a spatial as well as a temporal heterogeneity, revealing that JT are highly unstable, showing great variation in the size of donor segment. The breaks at the recipient chromosomes were mapped within the subtelomeric regions. The general telomere length was not affected and an underlying replication error resulting in microsatellite instability was excluded. We conclude that the emergence of JT is unlikely to cause fusion genes or to affect the expression of genes located in the breakpoint regions. The identification of YACs spanning the breakpoints, ie, YACs 913c7, 937g5, 948c2 and 955g1, may facilitate the isolation of DNA sequences leading to a genetic instability associated with the origin of multiple translocations.

show abstract

Interstitial telomeric sequences at the junction site of a jumping translocation

Cited by 58 publications

References 13 publications

Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability

Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability

Karyotypic dissection of Hodgkin's disease cell lines reveals ectopic subtelomeres and ribosomal DNA at sites of multiple jumping translocations and genomic amplification

Molecular characterization of jumping translocations reveals spatial and temporal breakpoint heterogeneity

Contact Info

Product

Resources

About