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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetics studies have suggested that short arm deletion in chromosome 1 is involved in triggering colorectal tumor development. To elucidate the role of 1p under-representation in the tumoral process, we investigated by fluorescence in situ hybridization interphase cytogenetics, using simultaneously centromeric and p36 telomeric probes for chromosome 1, 27 primary adenocarcinomas, 5 metastases, 5 adenomas and as control 4 normal mucous membranes. The 1p under-representation in paradiploid tumoral cells, interpreted as a 1p deletion, was observed in 8/27 adenocarcinomas, 2/5 metastases and 3/5 adenomas. Thus, in diploid cells 1p deletion was observed in some tumors independently of the stage of the process. The 1p under-representation in total number of examined cells, i.e., diploid and aneuploid, was observed in 14/16 grade B1-B2 tumors, in 5/8 grade C1-C2 tumors, and all grade D tumors (3/3) and all metastases (5/5). There were no correlations with location or histological characteristics of cancers, gender or age of patients. These results show high frequency of 1p under-representation in intestinal tumors, and lead to separate the under-representation of 1p in diploid cells, which correspond to a 1p deletion probably implicated in the initiation of the process, from the under-representation in aneuploid cells, which mainly may be the consequence of complex rearrangements in relation to extension of the malignant process.
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PMID:Distal deletion of 1p in colorectal tumors: an initial event and/or a step in carcinogenesis? Study by fluorescence in situ hybridization interphase cytogenetics. 1116 22

Normal cells in culture divide a certain amount of times and undergo a process termed replicative senescence. Telomere loss is thought to control entry into senescence. Activation of telomerase in tumors bypasses cellular senescence and is thus a requirement for tumor progression. We reported previously the preferential incorporation of 3'-azido-2', 3'-dideoxythymidine (AZT) in telomeric sequences of immortalized cells in culture. In this work, we have investigated the effects of chronic in vitro AZT exposure on F3II mouse mammary carcinoma cells. We demonstrate, for the first time, that AZT-treated tumor cells have a reduced tumorigenicity in syngeneic BALB/c mice. Tumor incidence was reduced and survival was prolonged in animals inoculated with AZT-treated cells when comparing with control counterparts. The number and size of spontaneous metastases were also decreased in animals inoculated with AZT-treated cells. In addition, we present evidence of morphological and biochemical signs of senescence, as shown by the staining for senescence associated beta-galactosidase activity, and induction of programmed cell death, as demonstrated by an increase of caspase-3 activity, in tumor cells exposed to AZT. These data indicate that chronic exposure of mammary carcinoma cells to AZT may be sufficient to induce a senescent phenotype and to reduce tumorigenicity.
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PMID:Chronic in vitro exposure to 3'-azido-2', 3'-dideoxythymidine induces senescence and apoptosis and reduces tumorigenicity of metastatic mouse mammary tumor cells. 1126 35

Relevant prognostic factors for head and neck squamous cell carcinoma are tumor extension (pT), occurrence of lymph node metastases (pN) and grade of differentiation (G). We tried to correlate these histological characteristics with numerical aberrations of whole chromosomes as demonstrated by fluorescence in situ hybridization techniques (FISH). Therefore, we investigated isolated interphase cells from paraffin sections of squamous cell carcinomas of the head and neck region from 46 patients with centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumor samples showed aneuploidy for most chromosomes analyzed. The main chromosomal abnormality was loss of chromosomal material, predominantly of chromosomes 3 (28%), 6 (20%), 9 (26%), 10 (24%) and 18 (33%). Multiple deletions could be demonstrated more frequently in poorly differentiated carcinomas (88% G3-tumors with more than one deletion in contrast to 66% G2-tumors). The occurrence of multiple deletions may also correlate with progression in lymph node metastasis (66% in pN0-tumors vs. 85% in pN2-tumors), whereas the differences between the stages of primary tumor extension were not so obvious. Despite of a some-what disproportionate distribution of tumors in the different pT- and pN-stages and the rather low number of cases, our results suggest a relationship between the quantity of chromosomal underrepresentation, grade of differentiation and higher lymph node stage. Therefore, they underline the importance of chromosomal deletions as a possible additional prognostic marker in head and neck squamous cell carcinoma.
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PMID:Multiple chromosomal underrepresentations detected by interphase cytogenetics - possible prognostic markers in head and neck tumors? 1134 17

Classical midgut carcinoids are rare intestinal neuroendocrine tumors that often present with metastases at diagnosis. In contrast to foregut carcinoids, midgut carcinoids are not related to the multiple endocrine neoplasia type 1 syndrome, and the mechanisms involved in their tumorigenesis are unknown. Eight classical midgut carcinoids were analyzed by genome-wide screening for loss of heterozygosity. Deletions on chromosome 18 were found in 88% of the tumors. DNA sequencing and immunohistochemical staining for Smad4/DPC4, which often is homozygously mutated in pancreatic and colon carcinomas, revealed no aberrations. In 1 tumor, a region telomeric to the Smad4/DPC4/DCC genes at 18q21 was deleted. Other chromosomes were affected in 3 lesions only. The high frequency of chromosome 18 deletions strongly indicates a genetic alteration of importance in classical midgut carcinoid tumorigenesis, apparently not involving the Smad4/DPC4 gene.
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PMID:Chromosome 18 deletions are common events in classical midgut carcinoid tumors. 1135

Genetic changes underlying the aggressive progression of human cutaneous melanoma are not completely understood. In order to characterise genetic alterations associated with the metastatic behaviour of this neoplasm we used comparative genomic hybridisation (CGH) in combination with fluorescence in situ hybridisation (FISH) on an experimental metastatic model of three related human melanoma cell lines. Tumour lines were selected based on their various metastatic capacity to liver in immunosuppressed mice. The parental cell line (A2058) was a human amelanotic melanoma cell line, adaptation of this line to in vivo growth as xenograft the HT168 tumour and its cell line was established. After intrasplenic transplantation of HT168 cells into immunosuppressed mice, a highly metastatic variant (HT168-M1) was selected. Several chromosomal aberrations common to all three lines indicating common clonal origin, as well as additional non-shared chromosomal changes were found. The original cell line (A2058) exhibited the highest number of genetic changes. Chromosomal alterations present only in the highly metastatic line (HT168-M1) involved losses on chromosome 4, 9p21.3-pter and 10p. Chromosome copy number patterns and the nature of chromosome 4 loss were further investigated by FISH using different centromeric probes and a chromosome 4 painting probe. According to our CGH and FISH results we assume that alterations present only in the aggressive metastatic subline are associated with the increased - metastatic potential. Our observations further support the hypothesis, based on some recently published data, that certain (so far unidentified) suppressor genes having an important role in tumour progression are located on these chromosomes.
Clin Exp Metastasis 2000
PMID:Liver metastatic ability of human melanoma cell line is associated with losses of chromosomes 4, 9p21-pter and 10p. 1144 59

Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) play an important role in a variety of malignant neoplasias, making the search for aberrations in the relevant chromosomes an important issue. Differential expression of the EGFR gene was investigated by reverse transcriptase (RT)-PCR on tissue samples of normal skin, nevi, primary melanomas, and melanoma metastases. The EGFR gene is located on chromosome 7p12.3-p12.1. To determine the number of chromosomes 7 in cell nuclei of the mentioned tissue samples we performed fluorescence in situ hybridization (FISH) on touch preparations, using a DNA probe that hybridizes specifically to the centromeric region of chromosome 7. Additionally, chromosome 7 number in interphase nuclei was determined in short-term primary cell cultures of nevi, primary melanomas, and metastases. The highest EGFR gene expression frequency was found in melanoma metastases. By FISH we detected the highest fraction of cell nuclei with more than two chromosomes 7 in the group of metastases. Our results suggest that overexpression of the EGFR gene might play an important role in metastasis of malignant melanoma. This is well reflected by polysomy 7, possibly accounting for an increased EGFR gene copy number.
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PMID:Chromosome 7 aneusomy. A marker for metastatic melanoma? Expression of the epidermal growth factor receptor gene and chromosome 7 aneusomy in nevi, primary malignant melanomas and metastases. 1149 18

Characteristic genetic changes underlying the metastatic progression of malignant melanoma is incompletely understood. The goal of our study was to explore specific chromosomal alterations associated with the aggressive behavior of this neoplasm. Comparative genomic hybridization was performed to screen and compare genomic imbalances present in primary and metastatic melanomas. Sixteen primary and 12 metastatic specimens were analyzed. We found that the pattern of chromosomal aberrations is similar in the two subgroups; however, alterations present only in primary and/or metastatic tumors were also discovered. The mean number of genetic changes was 6.3 (range 1-14) in primary and 7.8 (range 1-16) in metastatic lesions. Frequent losses involved 9p and 10q, whereas gains most often occurred at 1q, 6p, 7q, and 8q. Distinct, high-level amplifications were mapped to 1p12-p21 and 1p22-p31 in both tumor types. Amplification of 4q12-q13.1, 7q21.3-qter and 8q23-qter were detected only in primary tumors. The 20q13-qter amplicon was present in a metastatic tumor. The number of genetic alterations were significantly higher in primary tumors which developed metastases within one year after the surgery compared to tumors without metastasis during this time period. Fluorescence in situ hybridization with centromeric and locus-specific probes was applied to validate CGH results on a subset of tumors. Comparison of FISH and CGH data gave good correlation. The aggressive behavior of melanoma is associated with accumulation of multiple genetic alterations. Chromosome regions, which differ in the primary and metastatic lesions, may represent potential targets to identify metastases-related chromosomal alterations.
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PMID:Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization. 1151 55

For several reasons, chromosome 3p is thought to be involved in the pathogenesis of sporadic endocrine pancreatic tumours (EPTs): von Hippel-Lindau's disease (VHL gene at 3p25.5) is associated with EPTs; 3p is frequently involved in solid human tumours; and comparative genomic hybridization has identified frequent losses at 3p in EPTs. This study investigated 99 benign and malignant tumours, including 20 metastases, from 82 patients, by microsatellite loss of heterozygosity (LOH) analysis and fluorescence in situ hybridization (FISH) in order to evaluate the importance of chromosome 3p deletions in the molecular pathogenesis and biological behaviour of EPTs, to elaborate a common region of deletion, and to narrow down putative tumour suppressor gene loci. Allelic losses of 3p were found in 58/99 (58.6%) of tumours in 45/82 (54.9%) patients; analysis of seven microsatellite markers (3p26-p21) revealed a common region of LOH at 3p25.3-p23. The LOH frequency was significantly higher in malignant than in benign neoplasms (70.2% versus 28.0%; p=0.001). In addition, a strong correlation was found between the loss of alleles on chromosome 3p and clinically metastatic disease (LOH of 73.7% in metastasizing versus 41.5% in non-metastasizing tumours; p=0.008). EPTs from these patients showed a tendency towards losing large parts or the entire short arm of chromosome 3 with tumour progression. Furthermore, FISH analysis revealed complete loss of chromosome 3 in ten out of 37 EPTs (27%). These results indicate that a putative tumour suppressor gene at 3p25.3-p23 may play a role in the oncogenesis of sporadic EPTs and that losses of larger centromeric regions are associated with metastatic progression.
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PMID:Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression. 1152 53

Deletions of regions at 13q14 have been detected by various genetic approaches in human cancers including prostate cancer. Several studies have defined one region of loss of heterozygosity (LOH) at 13q14 that seems to reside in a DNA segment of 7.1 cM between genetic markers D13S263 and D13S153. To define the smallest region of overlap (SRO) for deletion at 13q14, we first applied tissue microdissection and multiplex PCR to detect homozygous deletion and/or hemizygous deletion at 13q14 in 134 prostate cancer specimens from 114 patients. We detected deletions at markers D13S1227, D13S1272, and A005O48 in 13 (10%) of these tumor specimens. Of the 13 tumors with deletions, 12 were either poorly differentiated primary tumors or metastases of prostate cancer. To fine-map the deletion region, we then constructed a high-resolution YAC/BAC/STS/EST physical map based on experimental and database analyses. Several markers encompassing the deletion region were analyzed for homozygous deletion and/or hemizygous deletion in 61 cell lines/xenografts derived from human cancers of the prostate, breast, ovary, endometrium, cervix, and bladder, and a region of deletion was defined by duplex PCR assay between markers A005X38 and WI-7773. We also analyzed LOH at 13q14 in the 61 cell lines/xenografts using the homozygosity mapping of deletion approach and 26 microsatellite markers. We found 24 (39%) of the cell lines/xenografts to show LOH at 13q14 and defined a region of LOH by markers M1 and M5. Combination of homozygous or hemizygous deletion and LOH results defined the SRO for deletion to be an 800-kb DNA interval between A005X38 and M5. There are six known genes located in or close to the SRO for deletion. This region of deletion is at least 2 Mb centromeric to the RB1 tumor-suppressor gene and the leukemia-associated genes 1 and 2, each of which is located at 13q14. These data suggest that the 800-kb DNA segment with deletion contains a gene whose deletion may be important for the development of prostate and other cancers. This study also provides a framework for the fine-mapping, cloning, and identification of a novel tumor-suppressor gene at 13q14.
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PMID:An 800-kb region of deletion at 13q14 in human prostate and other carcinomas. 1159 38

Amplification and overexpression of c-MYC is a common event in various neoplasias. Recently, comparative genomic hybridization (CGH) of primary pancreatic adenocarcinomas revealed a distinct high-level amplification of 8q23-qter, suggesting that c-MYC located on 8q24 may be a candidate oncogene. To evaluate the biological significance and prognostic value of c-MYC activation in pancreatic carcinoma, we performed interphase fluorescence in situ hybridization (FISH) and immunohistochemistry on a series of 69 primary pancreatic adenocarcinomas, 19 corresponding lymph node metastases, and 5 pancreatic intraductal lesions. Dual color FISH using a probe for c-MYC (8q24) and a centromeric probe for chromosome 8 revealed amplification of c-MYC in 32.3% and 29.4% of primary and metastatic tumors, respectively. Immunostaining identified c-MYC protein overexpression in 43.5% of primaries and 31.6% of metastases. Low concordance between positive FISH and immunostaining (13.4%) suggests multiple independent regulatory pathways of c-MYC activation. Statistical evaluation revealed significant correlation (alpha = 0.033) between c-MYC protein overexpression and histopathological tumor grade but absence of correlation with tumor stage or lymph node status. Analysis of pancreatic intraductal lesions showed c-MYC amplification and protein overexpression in two of five cases in which invasive carcinoma exhibited identical aberrations. We conclude that deregulation of c-MYC protein is common in pancreatic cancer and that it may be involved in early neoplastic development and progression rather than in locoregional spread of invasive cancer.
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PMID:c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: incidence, mechanisms, and clinical significance. 1195 Sep 22


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