An Increased Frequency of Numerical Chromosomal Abnormalities and 1p36 Deletions in Isolated Cells from Paraffin Sections of Malignant Melanomas by Means of Interphase Cytogenetics

Poetsch, Micaela; Woenckhaus, Christian; Dittberner, Thomas; Pambor, M; Lorenz, Gerd; Herrmann, Falko H.

doi:10.1016/s0165-4608(97)00471-8

Cited by 26 publications

(13 citation statements)

References 27 publications

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“…As the loss of 1p36 was first reported in NB by Brodeur et al (1977), studies have identified the deletion of this region in many other human malignancies such as brain tumor (Hashimoto et al, 1995), melanoma (Poetsch et al, 1998), leukemia (Mori et al, 1998), breast cancer (Bieche et al, 1998) and cervix cancer (Cheung et al, 2005), suggesting the presence of tumor suppressor gene(s) in this region. Chromosomal transfer experiments support such a hypothesis, as NB cell lines transfected with 1p DNA showed neuronal differentiation and suppression of tumorigenicity (Bader et al, 1991).…”

Section: Introductionmentioning

confidence: 93%

The MYCN oncogene is a direct target of miR-34a

et al. 2008

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Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCNamplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT-PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression profiling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR-34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma.

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Section: Introductionmentioning

confidence: 93%

The MYCN oncogene is a direct target of miR-34a

et al. 2008

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“…8,[13][14][15][16][17][18][19][20][21] After being mapped to the chromosomal region 1p35-1p36, p73 has been postulated to act as a tumor suppressor gene, as this region was shown to be deleted in several human malignancies including neuroblastoma, pheochromocytoma, oligodendroglioma, melanoma, merkel cell cancer, germ cell cancer, breast cancer, ovarian cancer, liver cancer and colon cancer as well as in some precancerous lesions like colorectal adenomas. 20,[22][23][24][25][26] Recently published preliminary data discussed the role of p73 in hematologic neoplasias, 27,28 as well as in renal cell carcinoma 29 and lung cancer. 23 Although initial analysis of neuroblastoma cell lines failed to reveal p73 mutations, Kaghad et al 6 suggested that monoallelic transcription of p73 and absence of protein expression in neuroblastomas with hemizygous 1p36 deletions were consistent with involvement in tumor development supporting the notion that p73 might act as a tumor suppressor gene in malignancies with 1p36 deletions.…”

Section: Introductionmentioning

confidence: 99%

Analysis of p73 and p53 gene deletions in multiple myeloma

et al. 1999

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Recently, p73, a protein with structural and functional similarities to p53, an extensively studied tumor suppressor gene, has been cloned. After being mapped to the chromosomal region 1p35-1p36, it has been postulated to act as a tumor suppressor gene, too, as this region is altered in several human malignancies. Deletions of the short arm of chromosome 1 have frequently been described in multiple myeloma (MM) whereas structural abnormalities of the 17p13 region including p53 are rare events in this disease. Since it has been proposed that especially neoplasias lacking p53 alterations might show a loss of heterozygosity at 1p35-1p36, we studied the frequency of p53 and p73 deletions in bone marrow mononuclear cells of 68 patients with MM, two patients with monoclonal gammopathy of undetermined significance and four patients with plasma cell leukemia. Dual-color fluorescence in situ hybridization (FISH) for p53 and p73 was performed using commercially available DNA probes for 17p13.3 and the microsatellite marker D1Z2, respectively. Centromeric DNA probes served to distinguish gene deletions from whole chromosome losses. In contrast to recently published FISH results, we only detected heterozygous p53 deletions in eight out of the 74 patients, three of them showing a monosomy 17. Heterozygous deletions of the D1Z2 region at 1p36 were found in six cases with one patient having a monosomy 1. Neither homozygous deletions of either chromosomal region nor nullisomies 1 or 17 could be detected. These results argue against a major role of p73 deletions in MM. As MM patients with 1p structural abnormalities have a significantly poorer survival rate than those with normal karyotypes, the role of other putative tumor suppressor genes located at the chromosomal region 1p36 in the pathogenesis of MM has to be determined.

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“…In our recent fluorescence in situ hybridization (FISH) studies, we were able to demonstrate deletions with a subtelomeric DNA probe hybridizing at the locus D1Z2 (1p36. 3) in a surprisingly high percentage of nodular melanoma samples [28,29]. These tumors represent melanomas with a high capacity to metastasize.…”

Section: Introductionmentioning

confidence: 99%

Significance of the small subtelomeric area of chromosome 1 (1p36.3) in the progression of malignant melanoma: FISH deletion screening with YAC DNA probes

et al. 1999

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The short arm of chromosome 1 (1p), especially the subtelomeric region of 1p36, is a common site for abnormalities in malignant melanoma of the skin. In a recent study nodular melanomas displayed deletions of 1p36 in an augmented percentage of cases. To evaluate the dimension of these deletions and to study their significance for the progression of malignant melanoma we analyzed seven melanoma cell lines, 32 primary tumors, and 32 metastatic tumors by fluorescence in situ hybridization with the DNA probe D1Z2 in 1p36.3 and eight YAC DNA probes hybridizing to 1p36, 1p32, 1p31, and 1p21. All cell lines, 91% of the metastatic tumors and 63% of nodular melanomas showed a deletion of 1p36.3. In the YAC hybridization experiments, the most frequent deletions were found in 1p36 in all cell lines, in 13% of nodular melanoma, and in 44% of metastatic tumors. Deletions in 1p36 were mostly confined to a rather small area near the locus D1Z2. The frequent occurrence of this deletion in melanomas with a high metastatic potential and the abundant accumulation of this deletion in metastasis point to genes located on 1p36, which might be of significance for the metastatic capability of malignant melanoma.

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An Increased Frequency of Numerical Chromosomal Abnormalities and 1p36 Deletions in Isolated Cells from Paraffin Sections of Malignant Melanomas by Means of Interphase Cytogenetics

Cited by 26 publications

References 27 publications

The MYCN oncogene is a direct target of miR-34a

The MYCN oncogene is a direct target of miR-34a

Analysis of p73 and p53 gene deletions in multiple myeloma

Significance of the small subtelomeric area of chromosome 1 (1p36.3) in the progression of malignant melanoma: FISH deletion screening with YAC DNA probes

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