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1.
Cancer Genet Cytogenet ; 31(1): 9-15, 1988 Mar.
Article in English | MEDLINE | ID: mdl-3162194

ABSTRACT

Fragile sites and nonrandom chromosome breakpoints in cancer cells are not distributed at random within the genome, but occur mainly in the light G-bands. If this nonrandom distribution is taken into account and a statistical analysis for the association of these two phenomena within the same chromosome band is carried out, based on the 400-band karyotype, no significant association is found between the common fragile sites and cancer breakpoints although there remains an association between the rare fragile sites and cancer breakpoints. These results, along with other chromosome mapping evidence that rare fragile sites are not at the breakpoint in some cancer chromosome rearrangements, cast serious doubt on any role for fragile sites in oncogenesis.


Subject(s)
Chromosome Fragility , Genetic Markers , Neoplasms/genetics , Chromosome Banding , Chromosome Fragile Sites , Humans
2.
Hum Genet ; 78(2): 144-7, 1988 Feb.
Article in English | MEDLINE | ID: mdl-3422214

ABSTRACT

A genomic probe homologous to 5.4 kb of the c-ets-1 gene was hybridized in situ to chromosomes expressing fra(11)(q23). This probe hybridized distal to the fragile site, which is just distal to the midpoint of band 11q23.3. This result localizes ETS1 from the FRA11B locus to 11q24. The result also distinguishes the FRA11B locus from the site of translocation at 11q23-q24 in the Ewing sarcoma- and peripheral neuroepithelioma-specific t(11;22), indicating that the chromosomes of a previously reported patient heterozygous for fra(11)(q23) did not rearrange at this fragile site to give rise to Ewing sarcoma. This adds to the mounting evidence against individuals with fragile sites being predisposed to developing cancer.


Subject(s)
Chromosome Fragility , Chromosome Mapping , Chromosomes, Human, Pair 11 , Proto-Oncogenes , Sarcoma, Ewing/genetics , Chromosome Banding , Chromosome Fragile Sites , Genetic Markers , Humans , Karyotyping , Nucleic Acid Hybridization
3.
Hum Genet ; 78(2): 134-6, 1988 Feb.
Article in English | MEDLINE | ID: mdl-2448221

ABSTRACT

The colony-stimulating factors regulate growth, differentiation, and function of blood cells. The effect of granulocyte colony-stimulating factor (G-CSF) on myeloid leukemias is unique among colony-stimulating factors in driving the leukemic cells from a self-renewing malignant state to a mature differentiated phenotype with the concomitant loss of tumorigenicity. This property of G-CSF has led to suggestions that its absence is responsible for lack of differentiation of leukemic cells and that the therapeutic administration of G-CSF could reverse this defect and result in a cure for leukemia. Here we show that the gene coding for human G-CSF is localized to chromosome 17, bands q11.2-21. The translocation of the long arm of chromosome 17 at q12-21 to chromosome 15 is a specific abnormality occurring in a high proportion of, if not all, patients with acute promyelocytic leukemia, a disease characterized by undifferentiated myeloid cells and a dismal prognosis. Abnormalities of the regulation of a specific differentiation factor gene mediated by a specific chromosomal rearrangement may be directly implicated in the pathogenesis of human leukemia.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 17 , Colony-Stimulating Factors/genetics , Leukemia, Myeloid, Acute/genetics , Translocation, Genetic , Granulocyte Colony-Stimulating Factor , Granulocytes , Humans , Karyotyping , Nucleic Acid Hybridization
4.
Genomics ; 2(2): 144-53, 1988 Feb.
Article in English | MEDLINE | ID: mdl-2900808

ABSTRACT

The fragile site, FRA16B, at 16q22.100 and four different translocations with breakpoints at 16q22.102, 16q22.105, 16q22.108, and 16q22.3 were used to locate and order DNA probes. This was achieved by Southern analysis of a somatic cell hybrid panel containing portions of chromosome 16 and by in situ hybridization. The anonymous DNA fragments D16S6, D16S10, and D16S11 were proximal to FRA16B and located at 16q13----q22.100. D16S4 and LCAT were located at 16q22.100----q22.102. TAT and HP were located at 16q22.105----q22.108. CTRB was located distal to 16q22.105 and therefore is in the distal half of 16q22. The order of markers in this region was determined as centromere-D16S6, D16S11, D16S10, MT-FRA16B-D16S4, LCAT-HP,TAT,CTRB-APRT- telomere. Linkage studies to determine map distances between the closest markers flanking the fragile site are now in progress.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 16 , DNA/genetics , Nucleic Acid Hybridization , Animals , Chromosome Fragile Sites , Chromosome Fragility , Chymotrypsinogen/genetics , Haptoglobins/genetics , Humans , Hybrid Cells , Karyotyping , Phosphatidylcholine-Sterol O-Acyltransferase/genetics , Translocation, Genetic , Tyrosine Transaminase/genetics
5.
J Med Genet ; 24(12): 761-6, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3430555

ABSTRACT

The regional localisation of the alpha globin (HBA) complex on the short arm of chromosome 16 was investigated by in situ hybridisation, Southern blot analysis, and linkage analysis using the fragile site at 16p12.3 (FRA16A) and translocation breakpoints within band 16p13.1. HBA was found to be distal to the two translocation breakpoints within band 16p13.1 and not closely linked to FRA16A. In situ hybridisation to the distal portion of the fragment on metaphase chromosomes expressing the fragile site and the observation of considerable recombination between FRA16A and HBA supports a localisation for HBA closer to the telomere than to FRA16A, at 16p13.2----pter.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 16 , Globins/genetics , Multigene Family , Genetic Linkage , Humans
6.
Hum Genet ; 77(2): 142-4, 1987 Oct.
Article in English | MEDLINE | ID: mdl-3477522

ABSTRACT

Multiple drug resistance has been shown to be associated with amplification/increased expression of a gene designated MDR. The localization of one member of the MDR gene family, MDR1, to the long arm of chromosome 7 by in situ hybridization is reported.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 7 , Drug Resistance/genetics , Chromosome Banding , Genetic Markers , Humans , Karyotyping , Nucleic Acid Hybridization
7.
Blood ; 70(1): 330-2, 1987 Jul.
Article in English | MEDLINE | ID: mdl-2439153

ABSTRACT

The human granulocyte-colony stimulating factor gene (G-CSF) is localized at 17q11.2-q21, the region of one of the breakpoints in the 15;17 chromosome translocation specific for acute promyelocytic leukemia (APL). As G-CSF induces differentiation and loss of tumorigenicity in myeloid leukemic cells or cell lines, it was possible that the translocation in APL involved the DNA of the G-CSF coding region or its regulatory region. In situ hybridization to chromosomes with the t(15;17) from patients with the APL translocation using a G-CSF cDNA clone revealed that the coding region of this gene is proximal to the t(15;17) breakpoint on chromosome 17. Southern analysis of DNA from patients with the APL translocation showed no differences in hybridization between normal and leukemic cells. These results indicate that the G-CSF coding sequence is not disrupted by the chromosomal rearrangement characteristic of APL.


Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 15/ultrastructure , Chromosomes, Human, Pair 17/ultrastructure , Colony-Stimulating Factors/genetics , Leukemia, Myeloid, Acute/genetics , Acute Disease , Adolescent , Aged , Base Sequence , Chromosome Mapping , Female , Granulocyte Colony-Stimulating Factor , Humans , Leukemia, Myeloid, Acute/pathology , Metaphase , Nucleic Acid Hybridization , Translocation, Genetic
8.
Science ; 236(4797): 92-4, 1987 Apr 03.
Article in English | MEDLINE | ID: mdl-3470945

ABSTRACT

There is much speculation about fragile sites on human chromosomes predisposing to specific chromosome rearrangements seen in cancer. Acute myelomonocytic leukemia is characterized by neoplastic chromosome rearrangements involving band 16q22 in patients who carry the rare fragile site at 16q22. This specific leukemic breakpoint is within the metallothionein gene cluster, which is here shown to be proximal to the rare fragile site (FRA16B) and to a common fragile site (FRA16C) in this region. Hence neither of these fragile sites are at the breakpoint in this leukemic chromosomal rearrangement.


Subject(s)
Chromosome Fragility , Chromosomes, Human, Pair 16 , Leukemia, Monocytic, Acute/genetics , Leukemia, Myeloid, Acute/genetics , Translocation, Genetic , Chromosome Fragile Sites , Chromosome Mapping , DNA, Neoplasm/genetics , Humans , Metallothionein/genetics
9.
Cytogenet Cell Genet ; 43(1-2): 10-3, 1986.
Article in English | MEDLINE | ID: mdl-3780312

ABSTRACT

The human adenine phosphoribosyltransferase gene (APRT) was mapped with respect to the haptoglobin gene (HP) and the fragile site at 16q23.2 (FRA16D). A subclone of APRT and a cDNA clone of HP were used for molecular hybridization to DNA from mouse-human hybrid cell lines containing specific chromosome 16 translocations. The APRT subclone was used for in situ hybridization to chromosomes expressing FRA16D. APRT was found to be distal to HP and FRA16D and was localized at 16q24, making the gene order cen-FRA16B-HP-FRA16D-APRT-qter.


Subject(s)
Adenine Phosphoribosyltransferase/genetics , Chromosome Fragility , Chromosomes, Human, Pair 16 , Haptoglobins/genetics , Pentosyltransferases/genetics , Animals , Cell Line , Chromosome Fragile Sites , Chromosome Mapping , Humans , Hybrid Cells/enzymology , Karyotyping , Mice , Nucleic Acid Hybridization
10.
Cytogenet Cell Genet ; 41(1): 38-41, 1986.
Article in English | MEDLINE | ID: mdl-3455911

ABSTRACT

The distamycin A-sensitive fragile site fra(16)(q22) is a precisely localized chromosomal marker. When expressed at metaphase, it visibly separates the chromosome material on either side of the fragile site. Using a cDNA probe encoding both the alpha and beta haptoglobin chains, the haptoglobin loci were found by in situ hybridization to be distal to fra(16)(q22).


Subject(s)
Chromosome Fragility , Chromosome Mapping , Chromosomes, Human, 16-18 , Haptoglobins/genetics , Chromosome Fragile Sites , DNA/genetics , Genetic Markers , Humans , Karyotyping , Nucleic Acid Hybridization
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