Localization of the oncogene c-erbA2 to human chromosome 3

The human c- erb Al gene has been previously mapped to chromosome 17. We have now mapped c- erb A2 to the short arm of chromosome 3, using a human genomic probe in Southern analysis of DNA from a panel of human/mouse somatic cell hybrids. In situ hybridization using the same probe on metaphase chromosomes has enabled fine chromosome mapping of c- erb A2 to the chromosome region 3p21-pter.     

Genetic mapping ofPim-1 putative oncogene to mouse chromosome 17

Pim-1 is a putative oncogene activated in T-cell lymphomas induced by Moloney and AKR mink cell focus forming (MCF) viruses. We have determined the chromosomal localization of the Pim-1gene in mice by Southern blot analysis of DNAs obtained from a panel of mouse-Chinese hamster somatic cell hybrids. The Pim-1gene was localized on chromosome 17, a chromosome frequently aberrant in T-cell lymphomas. Two chromosomal regions, containing sequences homologous to regions within the Pim-1locus, were localized on chromosome 6 and 16.     

A-raf oncogene localizes on mouse X chromosome to region some 10–17 centimorgans proximal to hypoxanthine phosphoribosyltransferase gene

The localization of the A-rafcellular oncogene on the mouse X chromosome has been determined using Xbal-restricted DNAs prepared from progeny of an interspecies backcross between the B6.CBA.R1 and the Spe/Pas mouse strains. This localization to the proximal part of the mouse X chromosome has been confirmed by the use of somatic cell hybrids, carrying partially deleted X chromosomes and suggests that the A-raf oncogene localizes to a region lying some 10–17 centimorgans proximal to the hypoxanthine phosphoribosyltransferase (Hprt) gene between the locus DXPas4and the locus DXPas7defined by the cross-reacting human X chromosome-specific probe DXS32 (M2C). This localization on the mouse X chromosome is compatible with the presence of the A-rafoncogene on the short arm of the human X chromosome between the centromere and Xp21.     

Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia

A reciprocal chromosomal translocation, t(15;17)(q22;q11.2-12), is characteristic of acute promyelocytic leukemia (APL) of French-American-British (FAB) subtype M3, and is not associated with any other human malignancy. The non-random pattern of the APL translocations suggests that specific genes on chromosomes 15 and 17 are somehow altered or deregulated as a consequence of the rearrangement. Translocation breakpoints in APL patients provide physical landmarks that suggest an approach to isolating the APL gene(s). Genetic and physical maps constructed for the APL breakpoint region on chromosome 17 have indicated that two fully-linked DNA markers, defining loci for THRA1 and D17S80, map to opposite sides of an APL breakpoint yet reside on a common 350-kb Clal fragment. Cosmid-walking experiments to clone this APL breakpoint have revealed a 38-kilobase deletion on chromosome 17. Studies in additional APL patients have shown that the breakpoint region on chromosome 17 spans at least 80 kilobases.     

The myeloperoxidase gene is translocated from chromosome 17 to 15 in a patient with acute promyelocytic leukemia

This study demonstrates that a differentiation-specific gene, the myeloperoxidase (MPO) gene, is translocated in a patient with acute promyelocytic leukemia (APL). The MPO gene recently has been mapped to chromosome #17, close to the breakpoint involved in the t(15;17) commonly seen in APL. By in situ hybridization, we showed that this gene was translocated from chromosome #17 to #15 in an APL patient. Although the significance of this translocation remains unclear, MPO is known to be highly expressed in APL. The causal relationship between the high expression and translocation of this gene requires further investigation.     

High resolution chromosome analysis of constitutional and acquired t(15;17) maps c-erbA to subband 17q11.2

High resolution chromosome analysis was performed on bone marrow cells from four patients with acute promyelocytic leukemia and t(15;17), and in lymphocytes from two unrelated, phenotypically normal persons with an apparently identical constitutional translocation. Scrutiny of prophase-prometaphase chromosomes localized the breakpoints in all six cases to subbands 15q22.3 and 17q11.2. Molecular genetic studies have localized the oncogene c-erbA to chromosome #17 between the breakpoints of the constitutional and the acquired anomaly. The present results, therefore, map c-erbA to subband 17q11.2.     

Two cases of acute promyelocytic leukemia with variant translocations: the importance of chromosome No. 17 abnormality

Two patients with acute promyelocytic leukemia (APL) were found to have chromosomal translocations in their leukemic cells; one had a 46,XX,t(7;17)(q36;q22) and another a 46,XY,t(1;17)(p36;q21) karyotype. These two cases of APL seem to be the first involving variant translocations instead of the standard t(15q+; 17q-) translocation. The present cases strongly suggest that the rearrangement of chromosome #17, which occurs in bands of the q21-22 region of the long arm, is crucially important in the pathogenesis of APL.     

Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia

The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocytic leukemia which was unusual in the sense of the occurrence of a myeloid-lymphoid conversion and lack of an apparent chronic phase. Cases 2 and 3 appeared to be de novo Ph+ ALL.     

Localization of the human homolog of the yeast cell division control 27 gene (CDC27) proximal to ITGB3 on human chromosome 17q21.3

The human homolog of theSaccharomyces cerevisiae cell division control 27 gene (CDC27) was mapped to human chromosome 17q12-q21 using a panel of human/rodent somatic cell hybrids and localized distal to the breast cancer susceptibility gene,BRCA1, using a panel of radiation hybrids. The radiation hybrid panel indicates that the most likely position of humanCDC27 on human chromosome 17 is between the marker D17S409 and the beta 3 subunit of integrin (ITGB3). Further confirmation of this localization comes from the sequence tagged site (STS) mapping of humanCDC27 to the same yeast artificial chromosomes (YACs) positive forITGB3. The estimated distance between ITGB3 and humanCDC27 is less than 600 kb.     

Localization of the 8;13 translocation breakpoint associated with myeloproliferative disease to a 1.5 mbp region of chromosome 13

There are five reported cases of an atypical myeloproliferative disorder in which the leukemia cells have a consistent t(8;13)(p11;q12) translocation. We analyzed the breakpoint in metaphases from two of these patients by fluorescence in situ hybridization using a series of yeast artificial chromosomes (YACs) derived from the 13q12 region. We found that a YAC containing the FLT1 and FLT3 oncogenes was localized distal to the 13q12 breakpoint and was not rearranged. YAC 66, a YAC that lies immediately adjacent to the chromosome 13 centromere, was localized proximal to the 13q12 breakpoint and was not rearranged. A third YAC, which is located between FLT1 and YAC 66, was unrearranged in normal metaphase chromosomes, but showed hybridization signals on both derivative chromosomes in both cases. Thus, the breakpoints in these two cases are localized to the same 1.5 Mbp region of 13q12. This may be the site of an unidentified gene involved in the pathogenesis of some types of leukemia.     

Central nervous system acute promyelocytic leukaemia: a report of three cases

Authors report 3 cases of acute promyelocytic leukaemia, in which the central nervous system was involved in the first period of relapse. The clinical features of these patients are discussed. Authors conclude that central nervous system involvement in acute promyelocytic leukaemia must be considered a very bad prognostic sign, because in these cases a rapidly progressive course may be expected.     

The occurrence of the 15;17 translocation in acute promyelocytic leukemia

For many years, acute promyelocytic leukemia (APL) has been associated with the 15;17 translocation. However, questions concerning an eventual geographic distribution have been raised by the Second and Fourth International Workshops on Chromosomes in Leukemia. Using a statistical approach, we showed that, even if the techniques of processing play an important role in detecting the 15;17 translocation, a geographic distribution exists, which is difficult to explain. Finally, we discuss the possible role of c-erb A1 in acute promyelocytic leukemia.     

Localization of a novel locus for hereditary nail dysplasia to chromosome 17q25.1-17q25.3

We report on a six-generation Pakistani consanguineous family with autosomal recessive transmission of a form of hereditary nail dysplasia. Affected individuals presented with onycholysis of fingernails and anonychia of toenails. Associated abnormalities of ectodermal appendages were not observed in any of the affected individuals. Linkage has been established to chromosome 17q. A maximum multipoint analysis logarithm of the odds ratio score of 4.85 was obtained at marker D17S1301. Due to the consanguineous nature of this kindred, the gene for nail dysplasia is probably contained within a 5.0-cM (3 MB on the sequence-based physical map) region of homozygosity flanked by markers D17S1807 and D17S937.