We performed cytogenetic studies on 58 patients with hairy cell leukemia (HCL) from 1975 to 1981. Analysable metaphase cells stained with Q-banding were obtained in 77 samples from 44 patients. Cells with abnormal chromosomes were found in both unstimulated and stimulated cultures of bone marrow and peripheral blood. Patients were classified in 6 groups. Group I, 2 patients with a clonal chromosome abnormality; group II, 13 patients with nonclonal structural abnormalities; group III, 5 patients with nonclonal numerical abnormalities; group IV, 19 patients with only a normal karyotype; group V, 15 patients with no or with fewer than 5 normal metaphase cells; group VI, 4 patients with questionable abnormal chromosomes. Common abnormalities were deletion of the long arm of No. 6 or +3 each in 3 patients, and +Y, +12 or +18 in 2 patients. Actuarial survival for each group was calculated from diagnosis and also from chromosome examination. The two patients with a clonal chromosome abnormality died within one year. Eight of 13 patients with nonclonal structural abnormalities died within 5 years after diagnosis, while none of 5 patients with nonclonal numerical abnormalities and 2 of 19 patients with normal chromosomes died within 5 years. The difference in the 5-year actuarial survival between patients with nonclonal abnormalities (groups II and III) and those with a normal karyotype was significant (p less than 0.05). The difference was more marked between patients with nonclonal structural abnormalities and those with a normal karyotype (p less than 0.01). Patients with nonclonal numerical abnormalities had a longer survival than those patients with nonclonal structural abnormalities (p less than 0.05). Thus, structural chromosome abnormalities in HCL may be a poor prognostic sign even when they are not clonal.

Bone Marrow↗

PubMedDate not supplied

Heritable fragile sites in cancer.

Explore the source record for details and available documents.

Chromosome Aberrations↗

PubMedDate not supplied

Evidence for two distinct c-src loci on human chromosomes 1 and 20.

A number of proto-oncogenes have recently been localized to the chromosomal segments that are the breakpoints in the specific rearrangements noted in human malignant diseases. Moreover, rearranged forms of several proto-oncogenes have been identified in malignant cells; in several instances, the proto-oncogene has undergone an alteration as a result of a nonrandom chromosomal rearrangement. One proto-oncogene that has yet to be associated with human neoplastic disease is c-src, the cellular homologue of the transforming sequence of Rous sarcoma virus (RSV). By somatic cell hybridization, c-src has been mapped to chromosome 20, but its precise location was not determined. We have now mapped this gene by using in situ hybridization of the cloned human c-src probe to human mitotic chromosomes. We report here that the human genome contains two loci with strong homology to the coding regions of this oncogene, at 1p34-p36 and 20q12-q13. It is noteworthy that these chromosomal regions are frequently involved in the structural rearrangements observed in haematological malignant diseases.

Avian Sarcoma Viruses↗

PubMedDate not supplied

Metallothionein gene cluster is split by chromosome 16 rearrangements in myelomonocytic leukaemia.

The metallothioneins (MTs) are a family of proteins of low relative molecular mass which bind heavy-metal ions. MTs exist in several molecular forms (MT-I, MT-II) and are encoded by a multi-gene family containing at least 14 closely related genes and pseudogenes. These proteins function in the regulation of trace-metal metabolism, the storage of these ions in the liver, and as a protective mechanism against heavy-metal toxicity. Somatic cell hybridization has shown that most MT genes, including the functional MT genes (MT1A, MT1B, MT2A), lie on human chromosome 16. Using in situ hybridization, we have now localized the MT genes to band q22 of chromosome 16. This chromosomal band is also a breakpoint in two specific rearrangements, the inv(16)(p13q22) and t(16; 16)(p13;q22) rearrangements, found in a subgroup of patients with acute myelomonocytic leukaemia (AMML). Hybridization of a MT probe to malignant cells from two patients with an inv(16) showed labelled sites on both arms of the inverted chromosome, indicating that the breakpoint at 16q22 splits the MT gene cluster. Similar results were obtained when this probe was hybridized to metaphase cells from two patients with a t(16; 16). These results suggest that the MT genes or their regulatory regions may function as an 'activating' sequence for an as yet unidentified cellular gene located at 16p13.

Chromosome Inversion↗

PubMedDate not supplied

Translocation of the p53 gene in t(15;17) in acute promyelocytic leukaemia.

Recent studies have demonstrated that the cellular tumour antigen p53 (ref. 1) can complement activated ras genes in the transformation of rat fibroblasts, suggesting that the gene encoding p53 may act as an oncogene. Here, by using in situ chromosomal hybridization, we have mapped the p53 gene to human chromosome 17, at bands 17q21-q22, the region containing one of the breakpoints in the translocation t(15;17) (q22;q21) associated with acute promyelocytic leukaemia (APL). Hybridization of p53 and erb-A (17q11-q12) probes to malignant cells from three APL patients indicated that the p53 gene is translocated to chromosome 15 (15q+), whereas erb-A remains on chromosome 17. Analysis of variant translocations demonstrates that the 15q+ chromosome contains the conserved junction, suggesting a role for p53 in the pathogenesis of APL. However, rearrangements of the p53 gene were not detected on Southern blotting of DNA from leukaemic cells of four APL patients with t(15;17).

Cell Line↗

PubMedDate not supplied

The human met oncogene is related to the tyrosine kinase oncogenes.

The met oncogene was previously isolated from a chemically transformed human cell line, MNNG-HOS. Recent evidence has demonstrated that two classes of transcripts are expressed from the met proto-oncogene locus. The met oncogene, however, expresses an aberrant RNA which has sequences in common with both transcripts. We now report partial nucleotide sequencing of the human met oncogene and show that met is related to the protein kinase oncogenes and growth factor receptors. The met nucleotide sequence is not identical to that of any published gene, and it is more closely homologous to the tyrosine kinases than to the serine/threonine kinases. Within the tyrosine kinase family, the sequenced met domains are most closely related to the human insulin receptor and the viral abl gene. In situ chromosome hybridization has mapped met to human chromosome 7 band 7q21-q31, a location distinct from that of other kinases. This is also a region associated with nonrandom chromosomal deletions observed in a portion of patients with acute nonlymphocytic leukaemia. The accompanying paper shows that this chromosomal locus is also tightly linked with the human heredity disease cystic fibrosis.

Base Sequence↗

PubMedDate not supplied

Cytogenetic and molecular analysis of pediatric neoplasms: diagnostic and clinical implications.

Recurring chromosome changes, particularly those closely associated with specific subtypes of tumors, have provided critical clues to the location of the genes involved in the genesis of these tumors. These, in turn, have led to the cloning of these genes, especially those located at translocation breakpoints in leukemias, lymphomas, and sarcomas. The immediate consequence of the cloning of these genes is to provide DNA probes for various diagnostic tests, including standard Southern blot analysis, the polymerase chain reaction, and fluorescence in situ hybridization. Because many of these chromosome rearrangements are associated with either an improved or a poorer survival, karyotypic abnormalities provide prognostic information. In the future, more sophisticated understanding of the genes involved and of the nature of their altered function should lead to improved therapy.

Acute Disease↗

PubMedDate not supplied

Chromosome changes in hematologic malignancies.

Evidence has now accumulated that chromosome changes are among the critical events that lead to malignant transformation of cells. More sophisticated analysis of clinical and cytogenetic parameters will lead to identification of additional subtypes of hematologic neoplasms such as t(15;17) APL or Ph1-positive CML. This differentiation has both diagnostic and prognostic importance. Cytogenetic studies currently in progress may reveal etiologic factors in malignant transformation; occupational exposure to potential mutagens, previous cytotoxic therapy, ethnic background, or a family history of cancer may correlate with specific chromosome abnormalities and specific subtypes of leukemia and lymphoma. As our knowledge of the human gene map increases, we expect to be able to relate changes in the affected chromosomes to biochemical abnormalities in the malignant cell. This will improve our understanding of how selected cells gain a proliferative advantage through malignant transformation, and it will aid in the precise classification of these diseases and thus lead to the design of more specific forms of therapy.

Chromosome Aberrations↗