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Results for “Chromosome Breakpoints”

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At least 19 recordsLinked to original sources
PubMed1978

A specific chromosome breakpoint associated with mouse plasmacytomas.

The chromosomes of uncultured cells of the near-diploid mouse plasmacytoma MOPC-31C were studied. The modal number of chromosomes was 44. The tumor lacked two marker chromosomes, reciprocal translocation [rcp t(12; 15)], that in previous studies were found to be common to 3 other uncultured myelomas and 1 cultured mouse myeloma. Through the formation of two markers, rcp t(6; 15), unique to this tumor, however, the tumor shared with other tumors and their specific markers a common breakpoint in chromosome "15 at band D3/E. This breakpoint has been found in all mouse plasmacytomas examined with banding thus far and is considered of possible importance in the development of this tumor.

Animals↗
PubMed1992

Relationship between chemical-induced fragile sites and chromosomal breakpoints in malignant cells in children.

Many fragile sites in the human genome occur at or near chromosomal breakpoints reportedly involved in translocations of DNA material in neoplastic cells. This fact has led some investigators to postulate that fragile sites have a pathogenic role in human neoplasia. To learn whether caffeine-induced fragile sites relate to breakpoints found in the neoplastic cells of an individual patient, we studied lymphocytes from the peripheral blood of 32 patients in remission from malignant disease. Lymphocytes were cultured in medium containing either 5-Fluoro-2'-deoxyuridine (FdU) or FdU plus caffeine, and G-banded metaphases were examined for nonrandom breaks. Analyses of completely G-banded malignant cell chromosomes from 31 of the 32 patients were available for comparison. In only once case, a 5-year-old child with acute lymphoblastic leukemia, did a caffeine-induced fragile site (1q44) coincide with a breakpoint in the neoplastic cells [dup(1)(q21-->q44)]. Our findings suggest that chromosomal abnormalities in childhood malignancies cannot generally be explained by the presence of FdU- or FdU plus caffeine-induced fragile sites.

Adolescent↗
PubMed1992

Mapping chromosomal breakpoints of Burkitt's t(8;14) translocations far upstream of c-myc.

To analyze the region upstream of c-myc, a number of novel probes were established. These were generated by chromosomal walking starting from the breakpoint of the chromosomal translocation of the B-cell line 380 and by cloning the breakpoint of the translocation of the Burkitt lymphoma cell line IARC/BL72. Using the newly isolated probes a detailed physical map of 500 kilobases of the region upstream of c-myc was established applying pulsed-field gel electrophoresis. The chromosomal breakpoint of IARC/BL72 cells was mapped to a site 55 kilobases 5' of c-myc. A region 20 kilobases in length and containing the breakpoints of 380, EW36, P3HR-1, and Daudi cells was identified 170-190 kilobases upstream of c-myc. In addition the HPV18 integration site in HeLa cells was located between 340 and 500 kilobases 5' of c-myc. The probes were used to define the c-myc amplification units in Colo320-HSR and HL60 cells as well as in four cases of small cell lung cancer. Evidence is provided that the amplicon of HL60 cells is discontinuously organized.

Base Sequence↗
PubMed1992

Isolation of cDNA sequences around the chromosomal breakpoint in a female with Lowe syndrome by direct screening of cDNA libraries with yeast artificial chromosomes.

The Lowe oculocerebrorenal syndrome (OCRL; McKusick 309000) is an X-linked disorder characterized by congenital cataracts, muscular hypotonia, mental retardation, and Fanconi syndrome of the renal tubules. A pair of yeast artificial chromosomes (YACs) that span the Xq25-q26 translocation breakpoint in a female with OCRL were used as probes to screen cDNA libraries made from bovine lens and human kidney. The methods used to prepare the YACs as probes and to screen the libraries are presented in detail. Two different transcripts were found that map to the region around the Xq25-q26 breakpoint. These transcripts are now being studied to determine whether one or the other is a candidate gene for OCRL.

Blotting, Southern↗
PubMed1992

Characterization of a 1.0 Mb YAC contig spanning two chromosome breakpoints related to Menkes disease.

Menkes disease, an X-linked recessive disorder of copper metabolism, has recently been mapped to Xq13.3 by two Menkes patients carrying chromosome rearrangements within this region. The breakpoints have been investigated by nonisotopic in situ suppression hybridization using YACs isolated from this region with the flanking markers DXS56 and PGK1. Three YACs were extending over the breakpoints at Xq13.3 and were shown to be overlapping by partial digest restriction maps, IRS-PCR fingerprinting and by the presence of common cosmid clones. These cosmids were subcloned and one of the single copy probes detected both breakpoints using rare-cutting restriction enzyme digests of the patients. All the results together localize the breakpoints to about 100 kb within the overlapping region of the YACs. Mapping of both breakpoints in a 1 Mb YAC contig implies that these YACs contain at least partially, the gene responsible for Menkes disease.

Chromosome Aberrations↗
PubMed1992

Sequence analysis of polymerase chain reaction amplified t(14;18) chromosomal breakpoints in formalin fixed, paraffin wax embedded follicular lymphoma.

AIMS: To determine whether junctional sequences of rearranged chromosomes can be amplified by use of the polymerase chain reaction (PCR) and whether direct sequence analysis of the PCR products is possible, using DNA from formalin fixed, paraffin wax embedded biopsy specimens. METHODS: DNA was extracted from paraffin wax embedded, formalin fixed lymphoma specimens, and junctional sequences of rearranged chromosomes were amplified by the PCR. The products were used as templates for asymmetrical PCR. Subsequently, direct sequence analysis was performed using the chain termination method. RESULTS: Formalin fixed, paraffin wax embedded biopsy specimens and PCR amplification could be used to determine the nucleotide sequences of junctional regions of rearranged chromosomes t(14;18) from patients with follicular lymphoma. CONCLUSION: The identification of junctional sequences of the translocation in follicular lymphoma provides a molecular "fingerprint" of t(14;18) of the lymphoma of an individual patient and can be used for the detection of clone specific DNA in any biopsy tissue obtained from the patient. The strategy used for rapid sequence analysis of PCR amplified DNA sequences will be useful in many areas of molecular pathology.

Base Sequence↗
PubMed1992

Herpes simplex virus and human papillomavirus sites correlate with chromosomal breakpoints in human cervical carcinoma.

The distribution of 1,912 breakpoints observed in a series of 148 cervical cancers was analyzed. Fifty bands were shown to be nonrandomly involved in chromosome structural rearrangements. One hundred thirty-three breaks were noted in bands known to contain a human papillomavirus integration site, and 454 breaks were noted in bands containing a herpes simplex virus breakage site. We suggest that herpes simplex viruses and, possibly, papillomaviruses play an important role in the carcinogenesis and/or development of cytogenetic abnormalities in cervical cancers.

Chromosome Aberrations↗
PubMed1992

A new chromosomal breakpoint in Ph positive, bcr negative chronic myelogenous leukemia. Report of a case.

We report a new case of Ph positive chronic myeloid leukemia (CML) without the classical rearrangement in Mbcr. By Southern blot analysis the molecular breakpoint was mapped 3 to 8 kb upstream of Mbcr. This region has not been shown to be rearranged in any other described case of CML. We did not detect any specific abnormal BCR-ABL transcript even with the use of the very sensitive RNA-PCR technique.

Base Sequence↗
PubMed1992

Partial trisomy for 5q and monosomy for 12p in a liveborn child as a result of a complex five breakpoint chromosome rearrangement in a parent.

A balanced complex chromosome rearrangement (CCR) involving four chromosomes is very rare and may lead to different types of aneuploid germ cells. We report a liveborn child with multiple congenital anomalies and an apparently balanced translocation, t(11;12). High resolution chromosome analysis in the mother showed a CCR involving chromosomes 5, 11, 12, and 16. In situ hybridisation showed that this CCR was the result of a five break rearrangement, and that the derivative chromosome 12 consisted of parts of chromosomes 5, 11, and 12. From this it could be deduced that the karyotype of the child was not balanced, but resulted in partial trisomy for 5q and partial monosomy for 12p. The clinical findings in the child were compatible with partial trisomy for 5q.

Abnormalities, Multiple↗
PubMed1992

Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14) translocation separate c-myc and the IgH locus up to several hundred kb.

In about 80% of Burkitt's lymphoma cases, the tumour cell harbours a reciprocal chromosomal translocation which invariably transposes the coding exons 2 and 3 of c-myc from chromosome 8 to the immunoglobulin heavy chain locus on chromosome 14. Those t(8;14) translocations which disrupt chromosome 8 within or close to the c-myc gene are well documented. In this study we have focussed on t(8;14) translocations with the chromosomal breakpoint far upstream of c-myc. We analyzed the breakpoint position in 44 BL cell lines with t(8;14) translocations of different geographical origin and identified 9 cell lines with the breakpoint more than 14 kb upstream of c-myc. In these cell lines the positions of the translocation junctions on the derivative chromosomes 8q- and 14q+ were mapped by pulsed field gel electrophoresis and multicolour fluorescence in situ hybridization. The breakpoints occur at distances between 55 and more than 340 kb upstream of c-myc with no preferential site on chromosome 8. On chromosome 14, however, the translocation breakpoints are clustered in a narrow region 5' of the intron enhancer of the immunoglobulin heavy chain gene. In 7 of 9 cases, the enhancer is fused to the c-myc bearing sequences of chromosome 8. In two cases, the translocation has occurred in switch mu and downstream of C mu, respectively. The impact of these results with respect to the hypothesis, that cis-regulatory sequences from the immunoglobulin heavy chain locus can deregulate c-myc expression in a manner sufficient for tumour formation, is discussed.

Base Sequence↗
PubMed1992

Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I.

We described cloning and characterization of an inversion breakpoint of chromosome 2 inv(2)(q35q37.3) observed in a patient with Waardenburg syndrome type I (WSI). Genomic cosmid clones containing the HuP2 gene, which was considered as a candidate for WSI, were isolated from a library constructed from the patient DNA. One of the clones contained the inversion breakpoint and revealed signals at both 2q35 and 2q37 by fluorescent in situ hybridization (FISH), indicating disruption of the HuP2 gene by the inversion. Our result further supports that the HuP2 gene is a candidate for Waardenburg syndrome type I and is located at q35.

Base Sequence↗
PubMed1992

Isolation of DNA markers from a region between incontinentia pigmenti 1 (IP1) X-chromosomal translocation breakpoints by a comparative PCR analysis of a radiation hybrid subclone mapping panel.

A strategy based on the use of human-specific interspersed repetitive sequence (IRS)-PCR amplification was used to isolate regional DNA markers in the vicinity of the incontinentia pigmenti 1 (IP1) locus. A radiation hybrid (RH) resulting from a fusion of an irradiated X-only somatic cell hybrid (C12D) and a thymidine kinase deficient (TK-) hamster cell line (a23) was identified as containing multiple X chromosome fragments, including DNA markers spanning IP1 X-chromosomal translocation breakpoints within region Xp11.21. From this RH, a panel of subclones was constructed and analyzed by IRS-PCR amplification to (a) identify subclones containing a reduced number of X chromosome fragments spanning the IP1 breakpoints and (b) construct a mapping panel to assist in identifying regional DNA markers in the vicinity of the IP1 locus. By using this strategy, we have isolated three different IRS-PCR amplification products that map to a region between IP1 X chromosome translocation breakpoints. A total of nine DNA sequences have now been mapped to this region; using these DNA markers for PFGE analyses, we obtained a probe order DXS14-DXS422-MTHFDL1-DXS705. These DNA markers provide a starting point for identifying overlapping genomic sequences spanning the IP1 translocation breakpoints; the availability of IP1 translocation breakpoints should assist the molecular analysis of this locus.

Animals↗
PubMed1992

Sublocalization of the chromosome 5 breakpoint of the 3;5 translocation in myelodysplastic syndromes and acute myeloid leukemia.

A t(3;5)(q25.1;q34) reciprocal translocation identifies a subset of cases of myelodysplastic syndrome or acute myeloid leukemia (AML) that are characterized by increased numbers of megakaryocytes and severe trilineage dysplasia. As a first step in characterizing the t(3;5) breakpoints, we asked whether the translocation involves the CSFIR/PDGFRB locus at 5q33-q35. Pulsed-field gel electrophoretic analysis of a region extending 580 kb 5' to the PDGFRB gene and 120 kb 3' to the CSFIR gene did not reveal aberrant restriction fragments in leukemic cell DNA, confirming that the breakpoint does not occur in the vicinity of these genes. To sublocalize the breakpoint, we performed Southern blot hybridizations using DNA from human x hamster somatic cell hybrids containing the normal 3, the normal 5, the derivative 3, or the derivative 5 human chromosome. Using a series of polymorphic DNA probes from the long arm of chromosome 5, which have been linked by genetic recombination, we bracketed the breakpoint to within a region that spans approximately 13 centimorgans (sex average) and is flanked by the q34-qter markers cKK5.19 and L1200 (D5S62). This analysis places the chromosome 5 breakpoint of the t(3;5) considerably telomeric to the CSFIR/PDGFRB locus, confirming our studies with pulsed-field electrophoresis. Future efforts to identify the genes affected by the t(3;5) should focus on the 5q segment described in this study.

Animals↗
PubMed2025

Subgenomic divergence and functional innovation following whole-genome duplication in Maleae species of Rosaceae.

Whole-genome duplication (WGD) drives plant evolution by inducing karyotype rearrangements and gene loss through subgenome fractionation. In this study, we investigate post-WGD evolutionary dynamics in Rosaceae, focusing on Maleae species, which uniquely experienced an additional WGD. Using phylogenetic and synteny analyses, we reveal that chromosomal breakpoints act as hotspots for localized fractionation, contributing to blurred homoeologous origins and influencing gene retention patterns. Here, we reconstruct karyotype evolution across Rosaceae subfamilies, highlighting chromosome reductions and lineage-specific rearrangements in Dryadoideae, Rosoideae, and Amygdaloideae. We also identify a bias for retaining transcription factors and hormone-related genes from older WGDs in subsequent polyploidy events. Transcriptome analysis classifies WGD-derived genes in Maleae species, such as apple and loquat, into three expression groups, with hormone-enriched genes playing roles in lignification and fruit-related innovations. These findings demonstrate the interplay between chromosomal breakpoints, biased retention, and functional divergence, revealing their contributions to genomic and phenotypic evolution in Maleae and their adaptive success within Rosaceae.

Genome, Plant↗
PubMed1992

Mapping of X chromosome translocation breakpoints in females with Duchenne muscular dystrophy with respect to exons of the dystrophin gene.

There are rare female patients who suffer from Duchenne or Becker muscular dystrophy because they carry an X;autosome translocation with a breakpoint in the dystrophin gene. We have defined the positions of seven of these breakpoints with respect to exon-containing HindIII fragments detected by dystrophin cDNA. One breakpoint lies between exon-containing HindIII fragments 7 and 8, five breakpoints between exon-containing HindIII fragments 31 to 41, and one lies close to exon-containing-HindIII fragment 50. The distribution of these and of a further seven translocation breakpoints whose positions are known is compared with that reported for deletions and duplications in affected males.

Animals↗
PubMed1992

Increased expression of 5q31 fragile site in a Bloom syndrome family.

In this work, we report spontaneous chromosomal breakpoints and fragile site expression induced by 5-fluorodeoxyuridine (FdUrd) and FdUrd plus caffeine in a family with Bloom's syndrome (BS) and 2 healthy donors. Standard and G-banded metaphases from each individual and each treatment were analyzed. Among the 59 common fragile sites (c-fra) identified in this work, only the frequency of 5q31 was significantly increased in the BS family with respect to healthy donors (P less than 0.005). A remarkable coincidence between the breakpoints involved in spontaneous chromosome aberrations and induced c-fra was found in BS homozygote patients. The importance of the interaction between fragile sites and chromosome rearrangements in cancer is discussed.

Bloom Syndrome↗
PubMed1992

Molecular epidemiology of Burkitt's lymphoma from South America: differences in breakpoint location and Epstein-Barr virus association from tumors in other world regions.

We have previously shown that the endemic (African) and sporadic (North American) forms of Burkitt's lymphoma (BL) differ at a molecular level. We have now extended our studies to the molecular epidemiology of BL in South America, specifically to two climatic regions: temperate (Argentina and Chile) and tropical (Brazil). We have examined the patterns of chromosomal breakpoint locations in 39 tumors with respect to geography and Epstein-Barr virus (EBV) association. The result of these analyses provide further support for the existence of pathogenetically distinct subtypes of BL in different world regions. The majority of breakpoints on chromosome 8 in South American BL (41%) occurred in the immediate flanking region of c-myc, ie, further 5' of the "typical" sporadic breakpoints, in the first exon/intron region, and further 3' of the "typical" endemic breakpoints, which are usually distant from c-myc. However, the distribution of breakpoints on chromosome 14 in tumors from the temperate and tropical regions of South America is similar to that observed in sporadic and endemic tumors. Interestingly, only one tumor with an unrearranged c-myc gene joined to the S mu region of chromosome 14 was observed. This combination was also rarely observed in our earlier series and presumably is either less readily generated by the mechanism that mediates 8;14 translocation or requires other, infrequent genetic changes to provide the necessary selective advantage for lymphomagenesis. The frequency of EBV association in South American BL (51%) is also intermediate with respect to tumors from the United States (30%) and Africa (100%). No correlation with the breakpoint location on chromosome 8 was discernable. Surprisingly, only 54% of tumors with breakpoint outside c-myc were EBV positive. This is in contrast to endemic tumors and suggests that any pathogenetic contribution of EBV is not dependent on breakpoint location, but is more likely to complement additional pathogenetic elements that differ in different world regions.

Adolescent↗