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Luba Trakhtenbrot

Publications and source records attributed to Luba Trakhtenbrot.

21 records · Page 2Linked to original sources

Interphase fluorescence in situ hybridization detection of chromosome 17 and 17q region gains in neuroblastoma: are they secondary events?

Gains of chromosome 17 and 17q region are the most frequent chromosomal abnormalities in neuroblastoma and have been associated with established prognostic indicators. Interphase fluorescence in situ hybridization (FISH) was used to define the status of chromosome 17 in near-triploid (3n) and near-diploid/tetraploid (2n/4n) primary tumors. Gains of chromosome 17 and 17q were detected in 22 and 26 tumors, respectively, in which the ploidy status was determined mainly by the copy number of chromosome 1. Four different types of gains were detected: gain of whole chromosome 17 (+17) and three partial gains (17q11.2 approximately qter, 17q21.1 approximately qter, and 17q21.3 approximately qter). The 17q11.2 approximately qter gains were found in both the 2n/4n and the 3n tumors. Gains of 17q21.1 approximately qter and 17q21.3 approximately qter were found only in the 2n/4n group, and the latter was involved always as a der(22)t(17;22)(q21;q13). A high association was found between chromosome 17 gains and 3n ploidy: +17 was detected in 93% of the 3n group and was not observed in the 2n/4n group. The +17 clone or clones were always present in combination with a clone with normal copies of chromosome 17 and, in the majority, with a +17q11.2 approximately qter clone. We conclude that interphase FISH is a sensitive method for detecting whole and partial chromosome 17 gains in neuroblastoma and can demonstrate the simultaneous presence of several clones with different status of chromosome 17 in 3n neuroblastomas. We suggest that chromosome 17 and 17q gains are not a primary event in the development of neuroblastoma.

Chromosome Aberrations↗

A role for common fragile site induction in amplification of human oncogenes.

Oncogene amplification is an important process in human tumorigenesis, but its underlying mechanism is currently unknown. Cytogenetic analysis indicates that amplification of drug-selected genes in rodent cells is driven by recurrent breaks within chromosomal common fragile sites (CFSs), via the breakage-fusion-bridge (BFB) mechanism. Here we show that BFB cycles drive the intrachromosomal amplification of the MET oncogene in a human gastric carcinoma. Our molecular evidence includes a "ladder-like" structure and inverted repeat organization of the MET amplicons. Furthermore, we show that the breakpoints, setting the centromeric amplicon boundaries, are within the CFS FRA7G region. Upon replication stress, this region showed perturbed chromatin organization, predisposing it to breakage. Thus, in vivo induction of CFSs can play an important role in human oncogenesis.

Centromere↗

Immature leukemic CD34+CXCR4+ cells from CML patients have lower integrin-dependent migration and adhesion in response to the chemokine SDF-1.

Chronic myelogenous leukemia (CML), a malignant myeloproliferative disorder originating from a pluripotent stem cell expressing the bcr-abl oncogene, is characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow (BM) into the circulation. Moreover, immature CD34+ CML cells have lower adhesion to stromal cells and fibronectin as well as lower engraftment potential in severe combined immunedeficient (SCID) and nonobese diabetic (NOD)/SCID mice than normal CD34+ cells. We report in this study that leukemic Philadelphia chromosome-positive (Ph+)CD34+ cells from newly diagnosed CML patients that express the chemokine receptor CXCR4 migrate in response to stromal-derived factor-1 (SDF-1). However, normal Ph-CD34+CXCR4+ cells derived from the same patient have significantly higher migration levels toward SDF-1. In contrast to their transwell migration potential, the SDF-1-mediated integrin-dependent polarization and migration of the Ph+CD34+CXCR4+ cells through extracellular matrix-like gels were significantly lower than for normal cells. Concomitantly, binding of these cells to vascular cell adhesion molecule-1 or fibronectin, in the presence of SDF-1, was also substantially lower. These findings suggest a major role for SDF-1-mediated, integrin-dependent BM retention of Ph+CD34+ cells.

Antigens, CD34↗