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Biomedical subjects

B K Hecht

Publications and source records attributed to B K Hecht.

At least 55 records · Page 3Linked to original sources
PubMed1988

Robertsonian chromosome recombinants are rare in cancer.

Whole-arm Robertsonian rearrangements are common constitutional changes of chromosomes that possess unusual properties. They occur spontaneously, are not inducible by ionizing radiation or clastogenic chemicals, show an exceptionally high meiotic mutation rate and nonrandom chromosome composition. A sample of 30 Robertsonian rearrangements in cancer patients revealed only three to have been acquired, none as a primary or significant secondary cancer chromosome change. The frequency of Robertsonian rearrangements is in the range of one per 1,100 at birth versus one acquired per 10,000 in cancer. Consistent with the prediction that Robertsonian rearrangements are recombinants, a subfamily of alpha satellite DNA displays selective homology between the centromeric regions of acrocentric autosomes proportional to their preferential entry into Robertsonian chromosomes. Recombination leading to Robertsonian rearrangements is common in meiosis, but is rare in mitosis. Hence, Robertsonian rearrangements are rare in cancer.

DNA, Satellite↗
PubMed1988

New common fragile sites.

We report the finding of a large number of new common fragile sites. Thirty-one (56%) of 55 common fragile sites found in a sample of human lymphocytes were ones not described at the Eighth International Workshop on Human Gene Mapping (HGM 8). The sample consisted of 3023 lymphocytes from nine unrelated individuals with a history of genitourinary malignancy. The lymphocytes were challenged in culture with aphidicolin (Apc), fluorodeoxyuridine (FUdR), 5-azacytidine (Aza), and bromodeoxyuridine (BrdU). Thirteen of the new common fragile sites were induced by Apc and FUdR, nine by Aza, five by BrdU, and four by combined means. The sites induced by Apc and FUdR were cross-induced by BrdU. The fragile sites induced by a diminished concentration of Aza were largely located in heterochromatic regions and were cross-induced by BrdU and FUdR. Exposure to BrdU for 24 hours, a technique hitherto restricted to rare fragile sites, induced several common fragile sites. Control lymphocytes had far fewer gaps and breaks, but these were clustered predominantly at high-expression fragile sites. Because more than half of the common fragile sites in this study were new, it is clear that much remains to be learned. Because the classes of fragile sites reveal cross-induction, we propose that fragile sites share structures in DNA.

Aphidicolin↗
PubMed1988

Regional chromosome localization of human papillomavirus integration sites near fragile sites, oncogenes, and cancer chromosome breakpoints.

The integration sites of human papillomavirus (HPV) DNA within the cervical carcinoma cell line C4-I and a primary cervical tumor were mapped by in situ hybridization. Cloned cellular sequences flanking the integrated viral DNA were used as probes. For the cell line, the viral integration site was mapped to chromosome region 8q21-q22.3, while in the primary tumor chromosome band 3p21 was the target for integration. The HPV DNA integration appears to occur in the vicinity of fragile sites, oncogenes, and chromosome breakpoints that are characteristic of hematologic malignancies and solid tumors. The integration of HPV may thus promote chromosome changes in cancer cells.

Cells, Cultured↗
PubMed1988

Deletion mapping of the beta-glucuronidase gene.

GUSB, the gene for beta-glucuronidase, has been localized to the proximal long arm of chromosome 7 between 7q11.2 and 7q22. Deficiency of beta-glucuronidase results in mucopolysaccharidosis type VII (MPS VII, Sly syndrome). The enzymatic defect has been demonstrated in cultured skin fibroblasts, leukocytes and serum of affected patients. An 8-yr-old boy presented with manifestations similar to MPS VII (mental retardation, short stature, "coarse" facial appearance, mild skeletal involvement and recurrent lower respiratory tract infection) but other, discrepant abnormalities, e.g., bilateral iris colobomata and cleft palate. Normal activity of beta-glucuronidase was found in the patient's leukocytes. Chromosome analysis disclosed an interstitial deletion of 7q with one breakpoint at the interface between bands 11.22 and 11.23 and the other breakpoint within band 21.1. DNA from this patient's leukocytes was analyzed for dosage of GUSB sequences. This locus appeared to be present at the normal diploid level. These findings suggest that GUSB is not in the portion of chromosome 7 deleted in our case, narrowing the smallest region of overlap to 7q21.1----7q22. We therefore assign the beta-glucuronidase gene to 7q21.1----7q22.

Child↗
PubMed1988

Prenatal diagnosis of a de novo unbalanced translocation (4p+) following in vitro fertilization.

We report herein a de novo unbalanced chromosome translocation in a fetus resulting from in vitro fertilization technology. Prenatal diagnostic analysis of an amniotic fluid revealed a 46,XX,4p+ karyotype. The origin of the extra material on the short arm of chromosome 4 could not be identified by a variety of banding techniques. However, examination of fetal parts did reveal some dysmorphic features.

Adult↗
PubMed1988

Fragile sites at 4q23 and 7q11.23 unique to bone marrow cells.

Fragile sites in chromosome bands 4q23 and 7q11.23 were discovered in bone marrow cells. Expression of these fragile sites was induced by treatment of the cells sequentially with 10(-7) M methotrexate and then 10(-5) M thymidine. No expression was observed in bone marrow cells without treatment. The fragile sites at 4q23 and 7q11.23 were seen individually, together, and in the homozygous state in a total of 20 bone marrow samples. The bone marrow karyotypes were normal in all cases. Expression of these common fragile sites at 4q23 and 7q11.23 could not be induced in blood lymphocytes from two subjects using methotrexate and thymidine, or by any other means including the addition of bromodeoxyuridine and fluoro-deoxyuridine or growth in folate-deficient medium. Because the fragile sites at 4q23 and 7q11.23 have never been observed in lymphocytes treated with methotrexate and thymidine for high-resolution chromosome analysis, it appears that these fragile sites are not expressed under these conditions in T lymphocytes. We propose that the differential expression of these fragile sites in bone marrow cells reflects genes active in bone marrow cells but not in blood lymphocytes.

Adult↗
PubMed1988

Fragile sites and genitourinary tumors.

We tested for fragile sites in lymphocytes from nine patients with genitourinary tumors to determine if a correlation existed between their cancer chromosome breakpoints and fragile sites. Induction was done for rare fragile sites in all known classes by exposure of cells to fluorodeoxyuridine and bromodeoxyuridine (BrdU). No rare fragile sites were found. Induction was also done for common fragile sites in all known classes using aphidicolin (Apc), 5-azacytidine, and BrdU. Although 56 common fragile sites were detected, only a single site corresponded in location to a genitourinary tumor chromosome breakpoint. That was the common fragile site in band 3p14. No overall correlation was found between fragile sites and chromosome rearrangements in carcinoma of the kidney, ureter, bladder, and testis. The sole known candidate for a possible biologic role is the 3p14 common fragile site in renal cell carcinoma.

Bromodeoxyuridine↗
PubMed1988

Loss of common 3p14 fragile site expression in renal cell carcinoma with deletion breakpoint at 3p14.

The common fragile site in human chromosome band 3p14 is a constant cytogenetic marker present on every normal chromosome #3. Therefore, we selected a renal cell carcinoma with a deletion breakpoint in 3p14 for analysis of the 3p14 fragile site. Aphidicolin was used to induce the expression of the 3p14 fragile site. The fragile sites expressed in the renal carcinoma cells generally mirrored those expressed in lymphocytes. The normal chromosome #3 in the renal carcinoma cells expressed the common 3p14 fragile site. The partially deleted #3 did not. The deletion breakpoint, therefore, cannot be beyond the 3p14 fragile site. The common fragile site in 3p14 must be at or very near the deletion breakpoint in 3p14 in renal cell carcinoma. These results are consistent with this fragile site causing this cancer chromosome deletion.

Aphidicolin↗
PubMed1988

Chromosome subband 17p11.2 deletion: a minute deletion syndrome.

Interstitial deletion of the short arm of chromosome 17 was detected in three unrelated patients with mental retardation and multiple congenital malformations. These patients were identified at a single centre over a six month period suggesting that del(17) (p11.2p11.2) is not a rare constitutional chromosome rearrangement. Comparison of the phenotypic features in a total of 19 patients with del(17)(p11.2p11.2) shows a consistent clinical phenotype with moderate to severe mental retardation, microbrachycelphaly, prominent forehead, broad face, flat midface, prognathism, short, broad hands, and behavioural anomalies such as self-mutilation. The sex ratio is unremarkable, parental ages are normal, and survival is usually unimpaired. Chromosome resolution of at least 500 bands appears necessary to detect this deletion.

Abnormalities, Multiple↗
PubMed1988

Chromosome sublocalization of a cDNA for human DNA polymerase-beta to 8p11----p12.

We have localized a cDNA fragment that codes for human DNA polymerase-beta. Using somatic cell and in situ hybridization techniques, this cDNA was cloned by screening a human KM-3 cell cDNA library in lambda gt 11 for expression of fused beta-galactosidase-human DNA polymerase-beta proteins. We have mapped this human polymerase-beta gene to the short arm of chromosome 8 in the subregion 8p11----p12.

Animals↗
PubMed1988

Clinical and biologic characterization of T-cell neoplasias with rearrangements of chromosome 7 band q34.

In T cell malignancy, rearrangements of chromosome 14 have been observed with a break in the band that contains the alpha chain gene for the T cell receptor (TCR). Because the beta chain TCR gene is in chromosome band 7q34, we searched for and report finding specific rearrangements of 7q34 exclusively in T cell malignancies. The rearrangements were reciprocal translocations between 7q34 and other points: 1p34, 9q32, 9q34, 15q22, and 19p13. The malignancies containing a 7q34 translocation were either T cell acute lymphoblastic leukemias or T cell lymphoblastic lymphomas that had similarities in clinical, enzyme, immunologic, and cellular characteristics. Hybridization using a probe to the beta-TCR gene disclosed unique rearrangements consistent with clonality in every case. A common pattern with chromosome breakpoints involving TCR genes may be emerging in T cell neoplasia.

Adenosine Deaminase↗
PubMed1988

Chromosomal localization of the human genes for lipocortin I and lipocortin II.

The human genes which code for Lipocortin I and Lipocortin II, proteins that inhibit phospholipase A2 (PLA2) activity, have been regionally localized in the human genome by chromosomal in situ hybridization and segregation analysis in somatic cell hybrids using cDNA clones for Lipocortin I and II. Lipocortin I, the 35 kd substrate for the epidermal growth factor (EGF) receptor/kinase, maps to chromosome region 9q11- greater than q22. The Lipocortin II cDNA probe detects at least four independently segregating loci which map to human chromosome regions 4q21-q31.1, 9pter-q34 proximal to c-abl, 10q proximal to 10q24 and 15q21-q22 proximal to the 15q22 translocation breakpoint characteristic of acute promyelocytic leukemia (APL). Thus, Lipocortin I and one locus detected by Lipocortin II cDNA are syntenic on chromosome 9; one Lipocortin II locus is perhaps not far from the genes for EGF and IL-2 on 4q; and another of the Lipocortin II loci is on 15q, perhaps not far from the APL breakpoint.

Annexins↗
PubMed1987

Fragile sites limited to lymphocytes: molecular recombination and malignancy.

Fragile sites on chromosomes are points at which rearrangements tend to occur nonrandomly. Because translocations between chromosomes #7 and #14 occur nonrandomly in normal cultured lymphocytes, we analyzed chromosomes #7 and #14 in 53,580 cultured lymphocytes and 109,300 other human cells. We found one rearrangement per 1,218 lymphocytes. These rearrangements were not restricted to translocations but included inversions and hitherto undetected duplications and deletions. In lymphocytes cultured for only 48 hours, rearrangements were seen indicating their presence in vivo. The breakpoints were exclusively in chromosome bands 7p13, 7q35, 14q11, and 14q32. The predisposition to form these rearrangements appeared nonrandom and inherited. These four bands act as if they contain fragile sites limited to lymphocytes. Fragility was not observed in these bands in cells from amniotic fluid, bone marrow, skin, or chorionic villi. Bands 7p13, 7q35, and 14q11 contain T-cell receptor (TCR) genes, whereas, band 14q32 contains the immunoglobulin heavy (IgH) chain locus. Rearrangements of these bands may result from molecular recombination between TCR or between TCR and IgH genes forming TCR/TCR and TCR/IgH chimeric genes important to understanding lymphocyte development and neoplasia. TCR/IgH chimeric genes have been found in T- and B-cell malignancy.

Chromosome Fragile Sites↗
PubMed1987

Chromosome changes connect immunodeficiency and cancer in ataxia-telangiectasia.

Ataxia-telangiectasia (AT) is a primary genetic immunodeficiency disease predisposing to cancer. Approximately 40% of patients with AT develop malignancy, usually of the lymphoid system. Increased chromosome breakage in AT leads to rearrangements such as translocations and inversions. The preferred chromosome breakpoints in AT involve genes in the immune system: the immunoglobulin (Ig) gene loci in chromosome bands 2p12, 14q32, and 22q11 and the T cell receptor (TCR) gene loci in chromosome bands 7p13, 7q35, and 14q11. Identical chromosome breakpoints are observed in chromosome rearrangements in normal T cells, Burkitt's lymphoma, and adult T cell leukemia. Molecular analysis of these chromosome rearrangements reveals recombination between an oncogene and Ig or between Ig and TCR. In AT, chromosome rearrangements connect the immune system to lymphoid cancer.

Adult↗
PubMed1987

Genetic history: II. The Cohens of London.

The genetic history in contemporary pedigree form is a useful tool for historical reading and study. The pedigree provides a guide to related personages and a data base for analysis. These points are illustrated by the family of Levi Barent Cohen, who came to London in the 18th century. There have been comparatively few consanguineous matings in the Cohen family. The family members have played central roles in Anglo-Jewish life in their own right and through marriage to other families such as the Montefiores and Rothschilds.

Female↗
PubMed1987

Y chromosome--specific DNA sequences in Turner-syndrome mosaicism.

Phenotypic females with Y-chromosomal material in their genome have an increased risk for development of gonadal malignancy. The detection and identification of Y-chromosomal material in these cases can be of critical importance for medical management. Chromosome analysis in four patients with Turner syndrome revealed the characteristic 45,X chromosome complement together with a second cell population containing a small marker chromosome (46,X, + mar). Molecular-hybridization analyses utilizing cloned, Y chromosome-specific DNA sequences were performed to determine whether Y-chromosomal material was present in each patient. Three cases contained some Y chromosome-specific sequences, whereas one case was negative with all four probes that we used. These results were compared with detailed cytogenetic studies--including G-, Q-, and G-11-banding--of the marker chromosomes. In one case in which Y chromosome-specific DNA sequences were demonstrated, the marker chromosome was G-11 negative. These results demonstrate that cytogenetic analysis alone can lead to misidentification of some Y chromosome-derived markers. The combination of cytogenetic and molecular analyses permits a more accurate characterization of anomalous Y chromosomes and in turn provides additional information that can be crucial to the correct medical management of Turner-syndrome patients.

Chromosome Banding↗