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Ninette Cohen

Publications and source records attributed to Ninette Cohen.

11 recordsLinked to original sources
PubMed2006

SKY analysis of childhood neural tumors and cell lines demonstrates a susceptibility of aberrant chromosomes to further rearrangements.

Malignant solid tumors are commonly characterized by a large number of complex structural and numerical chromosomal alterations, which often reflect the level of genomic instability and can be associated with disease progression. The aim of this study was to evaluate whether chromosomes that harbor primary aberrations have a higher susceptibility to accumulate further alterations. We used spectral karyotyping (SKY), to compare the individual chromosomal instability of two chromosome types: chromosomes that have a primary aberration and chromosomes without an aberration, in 13 primary childhood neural tumors and seven cell lines. We found that chromosomes that contain a primary aberration are significantly (p-value<0.001) more likely to gain further structural rearrangements or to undergo numerical changes (22.6%, 36 of 159 chromosomes) than chromosomes with no initial aberration (4.9%, 54 of 1099 chromosomes). These results are highly suggestive that aberrant chromosomes in solid tumors have a higher susceptibility to accumulate further rearrangements than "normal" chromosomes.

Aneuploidy↗
PubMed2006

An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism.

BACKGROUND: During a genetic study of autism, a female child who met diagnostic criteria for autism spectrum disorder, but also exhibited the cognitive-behavioural profile (CBP) associated with Williams-Beuren syndrome (WBS) was examined. The WBS CBP includes impaired visuospatial ability, an overly friendly personality, excessive non-social anxiety and language delay. METHODS: Using array-based comparative genomic hybridisation (aCGH), a deletion corresponding to BAC RP11-89A20 in the distal end of the WBS deletion interval was detected. Hemizygosity was confirmed using fluorescence in situ hybridisation and fine mapping was performed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. RESULTS: The proximal breakpoint was mapped to intron 1 of GTF2IRD1 and the distal breakpoint lies 2.4-3.1 Mb towards the telomere. The subject was completely hemizygous for GTF2I, commonly deleted in carriers of the classic approximately 1.5 Mb WBS deletion, and GTF2IRD2, deleted in carriers of the rare approximately 1.84 Mb WBS deletion. CONCLUSION: Hemizygosity of the GTF2 family of transcription factors is sufficient to produce many aspects of the WBS CBP, and particularly implicate the GTF2 transcription factors in the visuospatial construction deficit. Symptoms of autism in this case may be due to deletion of additional genes outside the typical WBS interval or remote effects on gene expression at other loci.

Agnosia↗
PubMed2005

Characterization of karyotypic events and evolution in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is cytogenetically characterized by a number of non-random events. However, knowledge is limited concerning the timing of occurrence and inter-action of many of these events. METHODS: Karyotypic patterns were obtained from a study group of 49 NB tumors that had been analyzed by conventional cytogenetics combined with FISH and in some instances SKY. RESULTS: All chromosomes were involved in a numerical and structural aberration in at least one tumor. There was a positive correlation between the occurrence of MYCN and del(1p) and between del(1p) and 17q. Aberrations involving chromosomes X, 3, 19, and del(1p) could be considered early events, whereas those involving chromosomes 9, 13, 15, 18, 20, and 21 were often late events. CONCLUSIONS: This study suggests that the karyotypic patterns characterizing NB are complex. There are aberrations that can be grouped into early or late karyotypic events, but others, such as gain of 17q, are variable.

Adolescent↗
PubMed2005

Acquisition of a Ph chromosome with minor BCR/ABL fusion in treatment-related myelodysplastic syndrome with chromosome 7 abnormalities in a patient treated for Hodgkin disease.

The patient reported in this study originally had Hodgkin disease that was treated heavily with multiple courses of combined chemotherapy and radiotherapy. Secondary myelodysplastic syndrome (MDS) with a complex karyotype with monosomy 7, deletion 7q31, and double deletion 7q31 developed 8 years later. During the course of the disease, conventional cytogenetics and interphase FISH (I-FISH) analysis detected a Ph chromosome and BCR/ABL fusion with mBCR rearrangement. Using a multiparametric cell scanning system that enables combined analysis with probes specific for 7/7q- and BCR/ABL in a single cell, we were able to demonstrate the presence of the BCR/ABL fusion only in cells with monosomy of chromosome 7 and 7q31 deletion, but not in cells with a normal chromosome 7 or with a double deletion of 7q31. We propose two possible models that may explain the appearance of the BCR/ABL fusion in the pre-existing treatment-related MDS clones characterized by chromosome 7 rearrangements.

Adult↗
PubMed2004

Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis.

Deletion of chromosome 13q is believed to be an adverse prognostic marker in patients with multiple myeloma (MM). Interphase fluorescence in situ hybridization (I-FISH) is the method of choice for detection of chromosome 13q deletion (del13q). However, I-FISH has high false-positive rates attributed to a low percentage of plasma cells (PC), which are responsible for MM, in bone marrow (BM) samples from MM patients. In an attempt to overcome this problem, combined morphologic and I-FISH analyses were performed by a unique system that allows rapid automatic scanning of a large number of cells with simultaneous determination of the lineage of specific cells carrying del13q. The percentage of PC with del13q in BM samples from 40 MM patients was calculated. In addition, we established a useful prognostic ratio defined as the number of PC with del13q divided by the number of non-PC with del13q (PDP/PDNP), which may help to precisely define the putative role of del13q in prediction response of MM patients to new therapeutic compounds. We suggest this technique as a novel sensitive and specific method for detection of del13q in a minor PC population of MM patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Karyotypic evolution pathways in medulloblastoma/primitive neuroectodermal tumor determined with a combination of spectral karyotyping, G-banding, and fluorescence in situ hybridization.

Medulloblastomas (MBs) or primitive neuroectodermal tumors (PNETs) represent 15%-30% of pediatric brain tumors and are the most common brain tumors in children; they are rare in adults. Classification of these tumors is based on tissue morphology and is often controversial and problematic. Karyotypic analysis of these tumors using conventional cytogenetic methods is often a difficult process that may be hindered by a limited number of metaphase cells and poor chromosome morphology, often leading to only partial characterization of the chromosomal abnormalities. We investigated three primary human tumors and four cell lines (CHO-707, DAOY, D-341, and PFSK) utilizing a combination of conventional G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH) techniques. A high level of intratumoral heterogeneity was seen, with multiple numerical and structural chromosomal aberrations. The chromosomes most frequently involved in structural aberrations were chromosomes 1 (14 rearrangements), 7 (9 rearrangements), and 21 (9 rearrangements). The chromosomes most frequently involved in numerical aberrations were chromosomes 1, 12, and 13 (four cases) and chromosomes 14, 17, 19, 21, 22, and X (three cases). Numerous aberrant chromosomes were characterized only with the SKY analysis, and based on these findings multiple clones were identified, facilitating analysis of karyotypic evolution. The most frequent evolution mechanism was via polyploidization, followed by acquisition of additional numerical or structural aberrations (or both); however, the results showed that the karyotypic evolution process in these tumors is typically divergent and complex.

Adult↗
PubMed2003

Clonal expansion and not cell interconversion is the basis for the neuroblast and nonneuronal types of the SK-N-SH neuroblastoma cell line.

The ability of neuroblastoma (NB) cells to interconvert bidirectionally, in vitro, from a neuroblast (N) to a nonneuronal (S) form is a well-studied biologic phenomenon of great clinical importance. Differences in the morphologic/ biochemical characteristics and gene expression patterns of the two cell populations have been investigated extensively in an effort to unravel the transdifferentiation process. Subcloning of the SK-N-SH NB cell line has led to two morphologically distinct cell types: SH-SY5Y (N-type) and SH-EP (S-type). Karyotypic analysis combined with G-banding and SKY showed a difference between these two cell types in the copy number of the 2p15 approximately pter segment, including the MYC-N gene. FISH analysis showed an extra copy of MYC-N present in all three lines: in SK-N-SH and SH-SY5Y the majority of cells had three copies of MYC-N, whereas in SH-EP the majority had two copies and only a small cell population with three copies was present. We suggest that the simultaneous coexistence of both cell types and the subsequent clonal expansion of one over the other is a possible explanation for the phenomenon observed and not the accepted interconversion model. According to the clonal expansion model, both N and S cells are simultaneously present in both cell lines. Under certain conditions, the less-aggressive S cells can dominate over the highly aggressive N cells, which eventually lead to the formation of the SH-EP and vice-versa.

Cell Differentiation↗
PubMed2002

SKY detection of chromosome rearrangements in two cases of tMDS with a complex karyotype.

In this study, we used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) as complementary techniques for the analysis of two therapy-related secondary myelodysplastic syndrome (t-MDS) cases with complex karyotypes, previously analyzed by G-banding. Different types of SKY's cytogenetic contributions include confirmation of G-banding results, identification of partially characterized rearrangements, identification of marker chromosomes unidentified by G-banding, and detection of cryptic reciprocal translocations. In particular, the ability of SKY to clarify a number of markers led to the comprehension of clonal evolution. The common aberration found in these two t-MDS cases was the fragility of chromosome 5 and monosomy of chromosome 18. We clearly present that the use of SKY combined with conventional G-banding analysis and FISH has assisted in the identification of important chromosomal events that may play a key role in the development of t-MDS.

Aged↗
PubMed2002

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↗
PubMed2002

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↗