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Biomedical subjects

O M Garson

Publications and source records attributed to O M Garson.

At least 55 records · Page 3Linked to original sources
PubMed1990

Breast cancer cytogenetics and beyond.

It is hypothesized that cancers arise as a result of genetic or chromosomal alteration. Evidence for this is provided by the leukaemias and lymphomas in which cytogenetic studies are of established value in diagnosis, classification and follow-up. In contrast, the cytogenetic study of all solid tumours, including breast carcinoma, is in its infancy. However, cytogenetic studies indicate that clonal structural alterations do occur, affecting several loci on a number of chromosomes. Molecular studies provide further evidence of recurring chromosomal breakpoints in breast cancer. This paper reviews the chromosomal rearrangements observed to date and discusses their relevance to the biology of breast cancer.

Breast Neoplasms↗
PubMed1989

Characterization of cell lines derived from a multiply aneuploid human bladder transitional-cell carcinoma, UCRU-BL-13.

A series of cultured cell lines (designated UCRU-BL-13) has been established from different serial passages of a multiply aneuploid human bladder transitional-cell carcinoma xenografted in nude mice. Serial passage of the xenografts in vivo and of the cell lines in vitro was accompanied by shifts in the tumor ploidy, with dominance of different major peaks. Despite this, the expression of tumor markers remained constant, and consistent chromosomal markers were observed both in the 8th xenograft passage and in a subline in tissue culture established over a year apart. Chromosomal numbers reflected the predominant aneuploid peaks observed; consistent numerical and structural changes included a marker derived from chromosome 1, 8p-, -10, 11q+, and 17q+. The cell line derived from the initial xenograft comprised a mixture of transitional, adenocarcinoma and squamous carcinoma cells in early passage, but adenocarcinoma cells were absent from later passages. The lines expressed the B-blood-group antigen, histocompatibility antigens, receptors for transferrin and EGF, and reacted with a series of monoclonal antibodies (MAbs) directed to malignant human epithelial cell lines. These lines provide a model for studying the evolution of tumor heterogeneity and drug resistance in bladder carcinoma exhibiting multiple aneuploidy.

Aneuploidy↗
PubMed1989

Six-year follow-up of the clinical significance of karyotype in acute lymphoblastic leukemia.

To evaluate the importance of pretreatment karyotype in predicting long-term outcome in acute lymphoblastic leukemia (ALL), we performed a follow-up study of the 329 patients from the Third International Workshop on Chromosomes in Leukemia. Living patients have now been followed a minimum of 6 years. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, rearrangements involving 8q24, t(4;11), 14q+, 6q-] or, in the remaining cases, modal number (less than 46, 46, 47-50, greater than 50). As previously reported for achievement and duration of complete remission, and overall survival, disease-free survival differed significantly (p less than 0.001) among chromosome groups for both adults and children. Among children, karyotype was an independent prognostic factor for predicting disease-free survival. Because of the long follow-up, we now have been able to utilize statistical models to estimate the percentage of patients cured, according to karyotype alone and combined with other risk factors. Adults with the highest likelihood of cure (21-33%) were those patients with FAB-L1, a leukocyte count of 50,000/microliters or less, and one of the following chromosome groups: greater than 50, 47-50, 6q-, or normal. In children these same characteristics were associated with the highest percentage of cure (58-71% cured). In addition, we identified several groups of children with less than 15% chance of cure who clearly need to be treated as high-risk patients at diagnosis. Future studies of patients who have received risk-adapted therapy based on these chromosome data are needed to determine if more intensive treatment will improve the outlook of patients with cytogenetically unfavorable types of ALL.

Adult↗
PubMed1989

Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse.

In order to investigate the cytogenetic patterns in relapsed acute myelogenous leukemia (AML), a clinical and cytogenetic follow-up of patients newly diagnosed for the Fourth International Workshop on Chromosomes in Leukemia (4IWCL) was evaluated at the 6IWCL. Information was received on 103 patients in relapse who were then classified into seven groups according to the diagnostic karyotype. These groups were: normal, t(8;21), t(15;17), +8, a single specific abnormality either numerical or structural other than those already listed, a single nonrandom or miscellaneous abnormality again either numerical or structural, and complex abnormalities. The patient's age, diagnostic FAB type, the number of relapses, the total survival time, and the karyotype in relapse were considered in each of these cytogenetic groups. The remission and survival rates were comparable in all groups except the +8 group, where patients relapsed earlier and had a shorter survival time. Multiple relapses occurred most frequently in the t(8;21) group, whereas none of the patients with t(15;17) relapsed more than once, although the total survival time was similar to the two groups. Thirty-nine percent of the patients relapsed with the same karyotype as at diagnosis. A more complex karyotype showing evolution was found in 53%, and 8% showed either a less-complicated karyotype or appeared to have reverted to normal. Numerical abnormalities in relapse frequently involved trisomy of chromosomes 8 and/or 21. There was a nonrandom development of 9q- with relapse in patients with t(8;21). A pericentric inversion of chromosome 4, and abnormality infrequently reported at diagnosis, was found in relapse in association with t(15;17), t(8;21), and +8 karyotypes. Changes considered to be typically secondary in nature involving 5q, 7q, and 12p were seen in only seven cases. Twenty-one patients who had an apparently normal karyotype at diagnosis remained normal in relapse, indicating that absence of clonal chromosome abnormality is a real observation in AML rather than a failure of detection.

Adolescent↗
PubMed1989

The proportion of erythroid mitoses in normal human bone marrow in short-term culture systems.

The proportion of erythroid cells in mitosis was determined in direct preparations and in synchronized and unsynchronized short-term cultures from normal human bone marrow. The stimulating effect on the proportion of erythroid mitoses of bovine serum albumin (BSA), erythropoietin (EP) and human leucocyte conditioned medium (HLC) derived from stimulated lymphocytes, was also analyzed in short-term marrow cultures. In synchronized and unsynchronized cultures, the proportion of erythroid mitoses was markedly lower than in direct preparations, with a mean of 75% in the direct compared to 11% in the unsynchronized cultures and 7% in synchronized. Statistical analysis showed that EP had a substantial influence on the erythroid cells while HCL had a minor effect.

Bone Marrow Cells↗
PubMed1989

Establishment and characterization of a childhood T-cell acute lymphoblastic leukemia cell line, PER-255, with chromosome abnormalities involving 7q32-34 in association with T-cell receptor-beta gene rearrangement.

A human leukemia cell line, PER-255, was established from the bone marrow of a 5-year-old boy with features typical of lymphomatous T-acute lymphoblastic leukemia (T-ALL). The leukemic origin of cell line PER-255 is indicated by its cytochemical and immunologic similarity to the patient's fresh leukemic cells, which correspond to immature cortical thymocytes. Southern blot analysis showed that the IgJH genes were in germline configuration, whereas both alleles of the T-cell receptor-beta (TCR-beta) gene were rearranged in PER-255 cells, with identical rearrangements present in the patient's leukemic cells. Cytogenetic analysis of the cell line revealed a single abnormal clone with the karyotype 46,XY,t(7;10)(q32-34;q24),t(9;12) (p22;p12-13). Reciprocal translocations involving chromosome bands 7q32-36, containing the gene for the TCR-beta chain, have been reported for a number of tumors of T-cell origin. Translocations involving the 7q32-36 region appear to be nonrandomly associated with childhood T-ALL, whereas abnormalities of 9p and 12p have been reported to be nonrandomly involved in ALL but not specifically associated with the T-cell phenotype.

Child, Preschool↗
PubMed1989

Acute lymphoblastic leukemia with a hypodiploid karyotype with less than 40 chromosomes: the basis for division into two subgroups.

This paper describes seven patients with ALL and a hypodiploid karyotype with less than 40 chromosomes. A consideration of these and 15 previously published cases indicates that they may be divided into two groups depending on chromosome number, i.e., less than 30 and 30-39. The less than 30 group are younger and predominantly female when compared with the 30-39 group, who are generally older than 40 years and mainly male. In addition, the two groups show different characteristic patterns of chromosome loss. Morphologically, both groups have populations of large and small lymphoblasts containing numerous small vacuoles, and both have common ALL antigen phenotypes. We present the possibility that the ALL patients in the less than 30 group are an example of an age restricted leukemia. There is insufficient data to assess any prognostic differences between the two patient groupings.

Adolescent↗
PubMed1988

Prospective study of childhood acute lymphocytic leukemia: hematologic, immunologic, and cytogenetic correlations.

We studied the karyotype in 81 consecutively diagnosed children with acute lymphocytic leukemia (ALL) treated at one institution on a randomized treatment protocol. In 75 patients (93%), a morphological cytogenetic result was obtained, and 57 (65%) were successfully G-banded. Of the 75 patients, 46 (61%) showed abnormal chromosomes, mainly hyperdiploidy and pseudodiploidy, and 29 had no detectable abnormality. Our findings confirmed that the karyotype has prognostic significance. Duration of complete remission was 93% at 42 months for patients with high hyperdiploidy (greater than 50). For patients with an apparently normal karyotype, it was 58%; and for patients with structural abnormalities it was 15%. The significance of these findings was confirmed by multivariate analysis, which showed age and karyotype to be the most important determinants of duration of remission.

Child↗
PubMed1988

Isodicentric X chromosomes involving the Xq13 breakpoint in myelodysplasia and acute nonlymphocytic leukemia.

Many nonrandom chromosome abnormalities, usually autosomal in nature, have been found to be associated with specific types of acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes (MDS). Specific abnormalities involving the sex chromosomes are rare. We have recently identified a structural abnormality of the X chromosome, for example, idic(X)(q13) in three patients: two with MDS progressing to ANLL and one with ANLL de novo. All three patients were elderly females with a very aggressive form of ANLL. Six other patients with a similar abnormality have been discovered in the literature; all having either MDS or ANLL and a short survival. It is suggested that the abnormality identifies a subset of MDS and ANLL occurring in elderly females.

Acute Disease↗
PubMed1988

Trisomy 4 in acute nonlymphocytic leukemia. An Australian case.

We report a case of acute nonlymphocytic leukemia, type M4 according to the FAB classification, whose cytogenetics showed trisomy 4 and multiple double minute chromosomes. The patient gave no history of exposure to toxic or carcinogenic substances.

Acute Disease↗
PubMed1988

Immunoglobulin allotypes Gm and Km in hematologic malignancies.

Immunoglobulin allotypes of the Gm and Km systems have been compared in patients with various forms of hematologic malignancies and healthy controls of the same ethnographic background. These comparisons found an increased frequency of the haplotype Gm and a decreased frequency of Gm in patients with Hodgkin's disease; a decreased frequency of Gm in diffuse, large-cell lymphoma patients; a decreased frequency of Gm and an increased frequency of Gm in acute myeloid leukemia patients; a decreased frequency of Gm in chronic myeloid leukemia patients, and an increased frequency of the phenotype Km(1+) in chronic lymphocytic leukemia patients. These results support previous suggestions of the involvement of immunoglobulin allotypes in the susceptibility to some forms of human hematologic malignancy.

Gene Frequency↗
PubMed1988

Interleukin-5 is at 5q31 and is deleted in the 5q- syndrome.

Human interleukin-5 (IL-5) is a selective eosinophilopoietic and eosinophil-activating growth hormone. By in situ hybridization this gene is mapped to chromosome 5q23.3 to 5q32. It is shown to be deleted in two patients with the 5q-syndrome and in one patient previously diagnosed with myelodysplasia whose condition had progressed to acute myeloblastic leukemia. The clustering of other genes involved in hematopoiesis (IL-3, granulocyte-macrophage colony-stimulating factor, feline sarcoma viral oncogene homolog, colony-stimulating factor 1) to the same region as IL-5 suggests a nonrandom localization and raises interesting questions concerning the evolution and regulation of these genes.

Aged↗
PubMed1987

Chromosome studies in inherited nonpolyposis colon cancer syndrome.

This study was designed to determine if any constitutional chromosomal markers were linked with the expression of colorectal neoplasms in the inherited nonpolyposis colon cancer syndrome, using a number of cytogenetic techniques. High resolution G-banding in 12 affected and 17 unaffected family members did not reveal a structural chromosome abnormality. Increased C-band heteromorphism was not seen in either affected or unaffected individuals, and no heritable fragile sites were detected. Mean baseline and mitomycin C-induced sister chromatid exchanges were not elevated in affected patients compared with controls. Mapping of sister chromatid exchanges did not reveal any hot spots of exchange. A tumor cell line with the karyotype 46,XY,der(13),t(13;?)(p11;?) was established from one patient, but no constitutional abnormality of chromosome #13 was found. In addition, 11 patients with familial polyposis coli were studied with high resolution G-banding and no heteromorphism of chromosome #2 in the region 2q21.3 was detected.

Cell Line↗
PubMed1987

Hybrid biphenotypic acute leukemia with extreme hypodiploidy.

A patient diagnosed as having acute lymphoblastic leukemia (L2) relapsed 4 months later and was found to have morphologic and immunologic evidence of a biphenotypic hybrid acute leukemia. Chromosome analysis at relapse showed two abnormal clones, one with marked hypodiploidy and the other with exactly double the hypodiploid clone. It is considered that this is an example of a hybrid lymphoblastic/nonlymphoblastic leukemia with unique karyotype.

Adult↗
PubMed1987

Localization of the G-CSF gene on chromosome 17 proximal to the breakpoint in the t(15;17) in acute promyelocytic leukemia.

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.

Acute Disease↗
PubMed1986

The multiple basal cell nevus syndrome: a cytogenetic study of six cases.

Six patients with typical features of the multiple basal cell nevus syndrome were studied cytogenetically, using prometaphase G-banding and C-banding. Three patients were from one family and the others were sporadic cases. No cytogenetic marker of the disease was identified using these techniques.

Adult↗