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Biomedical subjects

F Hecht

Publications and source records attributed to F Hecht.

At least 55 records · Page 3Linked to original sources
PubMed1989

Long-term growth of malignant thymocytes in vitro.

We report a new methodology for the long-term growth of malignant T-lymphoblasts from patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL). When malignant cells were cultured in the presence of insulin-like growth factor I under hypoxic conditions, cellular proliferation occurred that resulted in the establishment of immortal cell lines from ten of 12 patient tumors. Authenticity of each cell line was verified by a direct comparison of the immunophenotype, karyotype, and immunogenotype with the patient's tumor cells. This improved method of cell culture permits frequent establishment of cell lines from patients with T-ALL/T-LL, thereby aiding in analysis of thymocyte transformation and neoplasia.

Adolescent↗
PubMed1988

Chromosome rearrangements in dysplastic nevus syndrome predisposing to malignant melanoma.

The dysplastic nevus syndrome (DNS) is an autosomal dominant trait characterized by multiple atypical skin moles and a propensity to malignant melanoma. We studied chromosomes from a three-generation DNS family in 1977. Cells cultured from normal skin and dysplastic nevi showed an elevation in chromosome rearrangements with nonrandom breakpoints and clonal proliferation marked by chromosome change. The DNS qualifies as a chromosome instability disorder, the first known to manifest dominant inheritance and a clear discernible premalignant state. The DNS road to malignancy may logically proceed by genomic alterations including translocations, duplications, and deletions.

Chromosome Aberrations↗
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

Philadelphia chromosome-positive acute lymphoblastic leukemia cell lines without classical breakpoint cluster region rearrangement.

The Philadelphia (Ph) chromosome translocation which is classically observed in chronic myeloid leukemia (CML) is sporadically found in acute lymphoblastic leukemia (ALL). In CML the translocation breakpoint on chromosome 22 is within the breakpoint cluster region, while in childhood ALL, no detectable change in breakpoint cluster region is routinely observed. In order to investigate the nature of this difference, we have established and characterized two cell lines from a child with Ph positive ALL. The cell lines have retained the cytochemical staining pattern, enzyme activity, monoclonal antibody profile, and immunoglobulin gene rearrangements of the child's malignant cells. The cell lines had the same Ph translocation t(9;22) (q34;q11) as the child's malignant cells along with additional chromosome changes. Southern blot analysis showed that the Ph translocation did not involve the 5.8-kilobase breakpoint cluster region segment characteristically seen in CML. The cell lines reported here will be a valuable resource in ascertaining the biological significance of the Ph translocation seen in ALL.

Adenosine Deaminase↗
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, cancer chromosome breakpoints, and oncogenes all cluster in light G bands.

Fragile sites tend to be bands where breaks occur in cancer chromosome rearrangements that can involve oncogenes. The locations of fragile sites, cancer breakpoints, and oncogenes were therefore charted. All were predominantly in light G bands. Specifically, 78 of 89 (88%) fragile sites were in light G bands including the large group of common fragile sites inducible with aphidicolin (p less than 0.001). Of 61 cancer breakpoints, 50 (82%) were in light bands including translocation breakpoints (p less than 0.001). Thirteen of 14 (93%) oncogenes localized to light bands. The sharing of chromosome bands can stem from a biologically meaningful relationship, as between cancer breakpoints and oncogenes. Joint occupancy of chromosome bands can also reflect independent reasons to be in the same sector of the genome. Thus, fragile sites may well be in light bands because they are associated with active genes. This clearly does not rule out a biologic relationship between specific fragile sites and specific cancer breakpoints.

Chromosome Banding↗
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

Translocation t(3;8)(p14.2;q24.1) in renal cell carcinoma affects expression of the common fragile site at 3p14(FRA3B) in lymphocytes.

The common fragile site at 3p14(FRA3B) is cytogenetically close to the positions of translocation and deletion breakpoints frequently observed in renal cell carcinoma (RCC) and small cell carcinoma of the lung. Possible involvement of this fragile site in the familial RCC t(3;8)(p14.2;q24.1) was investigated. Expression of FRA3B, induced by treatment of lymphocytes with aphidicolin, is altered by the translocation. These results suggest that the fragile site is very close to, if not coincident with, the translocation breakpoint.

Aphidicolin↗
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↗