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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An unambiguous and rapid characterization of amplified DNA sequences in tumor cells is important for the understanding of neoplastic progression. This study was conducted to evaluate the potential of fluorescence in situ hybridization (FISH) to identify such amplified DNA sequences in human tumor cell lines. Applying this technique, we followed the metaphase location and interphase position of amplified DNA sequences corresponding to the SAMK, MYC, and MYCN genes in four cell lines derived from human tumors: two gastric carcinoma lines (KATO III and SNU-16), a neuroblastoma (NUB-7), and a neuroepithelioma (NUB-20) line. In metaphase cells of KATO III, NUB-7, and NUB-20 lines, the amplified regions were clearly visible and easily identified at an intrachromosomal location: in KATO III and NUB-7 at a terminal position and in NUB-20 at an interstitial position. In SNU-16, on the other hand, the amplified SAMK and MYC sequences were identified in extrachromosomal double minute chromosomes (DMs). In this line, the SAMK and MYC sequences were coamplified in the same cells and were colocated on the same DMs. FISH also allowed the identification of amplified DNA sequences in nondividing cells, enabling us to distinguish, at interphase, whether the amplification gave rise to intrachromosomal amplified regions (IARs) or to extrachromosomal DMs. The FISH technique also allowed us to determine at metaphase as well as at interphase the extent of amplification and the size of the IARs.
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PMID:Detection of amplified DNA sequences in human tumor cell lines by fluorescence in situ hybridization. 137 38

Gene amplification and related alterations in gene dosage were analyzed in a series of 34 cell lines derived from different human head and neck squamous cell carcinomas (SCCHN). INT2 gene amplification was observed in 62%, MYC gene amplification in 24%, and EGFR gene amplification in 21% of the cell lines. There was a strong correlation between EGFR gene amplification and increased copies of the ERBB2 gene on chromosome 17, suggesting a synergistic selection for these two genes either during cancer progression or in culture. Two abnormalities showed a significant correlation with clinical course: MYC gene amplification showed an inverse correlation with tumor recurrence (r = -0.44, p = 0.01), and a small increase in MYCL gene copies on chromosome I correlated with the presence of metastases (r = 0.61, p = 0.001). This altered MYCL gene dosage might represent a chromosome translocation rather than true gene amplification. In addition to gene amplification, 79% of the cell lines had increased copies of chromosome 8. Comparison of the cell lines with several of the corresponding primary tumors demonstrated that most gene amplifications were already present in the primary tumors, although some appeared de novo in cell culture. These studies indicate that gene amplification, especially of INT2, is a prominent abnormality in head and neck squamous cell cancer. Aneuploidy and chromosomal lesions other than gene amplification were also found to alter the dosage of several oncogenes specifically.
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PMID:Gene amplification and gene dosage in cell lines derived from squamous cell carcinoma of the head and neck. 138 84

We examined the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on EGF receptor (EGFR) phosphorylation and the expression of mRNAs for oncogenes, growth factors, their receptors and metalloproteinase genes by MKN-28 gastric carcinoma cells which express EGF, TGF-alpha and EGFR genes. Both EGF and TGF-alpha stimulated EGFR phosphorylation, EGF and TGF-alpha induced FOS, MYC and ERBB-2 oncogene expression. Interestingly, EGF increased the expression of mRNAs for TGF-alpha and EGFR. On the other hand, TGF-alpha increased TGF-alpha mRNA but decreased the expression of mRNAs for EGFR and TGF-beta. Furthermore, mRNAs for interstitial collagenase, stromelysin and procollagen type I genes were also enhanced after treatment with EGF and TGF-alpha. These results indicate that EGF and TGF-alpha successively evoke cascade phenomena which favor tumor progression, invasion and extracellular matrix formation, acting as autocrine growth regulators for gastric carcinomas.
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PMID:Induction of growth factor-receptor and metalloproteinase genes by epidermal growth factor and/or transforming growth factor-alpha in human gastric carcinoma cell line MKN-28. 216 68

The role of oncogenes in breast tumorigenesis is unclear. Alterations and/or amplification of several oncogene sequences have been observed in primary human breast tumors, in breast tumor cell lines, and in mammary tumors in model systems. In principle, such alterations could be sites of primary lesions for human breast cancer, causes of tumor progression or metastasis, or simply secondary lesions of highly aberrant tumor genomes. The present study tested genetic linkage of breast cancer susceptibility to nine oncogenes in 12 extended families including 87 affected individuals. Lod scores for close linkage of each candidate sequence to breast cancer were -19.6 for HRAS, -12.3 for KRAS2, -1.0 for NRAS, -6.0 for MYC, -6.1 for MYB, -8.2 for ERBA2, -7.9 for INT2, and -5.1 for RAF1. Regions of chromosome 11p associated with tumor homozygosity and the region of 3p carrying the gene for Von Hippel-Lindau disease could also be excluded from linkage to human breast cancer. The 5-kb allele of the MOS oncogene, previously proposed to be associated with breast cancer, was absent in these families, suggesting that polymorphism at this locus is not associated with inherited susceptibility. These results strongly suggest that oncogenes are not the sites of primary alterations leading to breast cancer. On the other hand, alterations in one or more of these sequences may be associated with tumor progression.
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PMID:Oncogenes and human breast cancer. 256 34

Oncogene amplification has been observed in various primary tumors and tumor-derived cell lines. In several types of cancer, amplification of specific oncogenes is correlated with the stage of tumor progression. To estimate the frequency of gene amplification in other tumor types and to determine whether the ability to grow in vivo is associated with gene amplification in tumor cell lines, we have developed a modified version of the in-gel renaturation assay that detects human DNA sequences of unknown nature amplified as little as 7- to 8-fold. This assay was used to screen 16 cell lines derived from various solid tumors and leukemias. Amplified DNA sequences were detected in only one cell line, Calu-3 lung adenocarcinoma. This cell line was found to contain coamplified NGL (formerly termed neu) and ERBA1 oncogenes. However, when one of the amplification-negative cell lines, PC-3 prostatic carcinoma, was selected for in vivo growth in nude mice, amplified DNA sequences became detectable in these cells. The amplified sequences included the MYC oncogene, which showed no amplification in the parental cell line but was amplified 10- to 12-fold in the in vivo-selected cells. MYC amplification may, therefore, provide tumor cells with a selective advantage specific for in vivo growth.
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PMID:Analysis of gene amplification in human tumor cell lines. 341 26

The transcription of human nm23 genes (nm23-H1, nm23-H2) is involved in suppression of tumor metastasis or tumor progression. Therefore the characterization of transcriptional regulatory mechanisms for both nm23 genes is very important. In this study we have isolated and analyzed the 5'-flanking region of the human nm23-H2 gene and estimated the distance to 4 kb between nm23-H2 and nm23-H1 genes. We localized the known microsatellite D17S396 within this region. Furthermore the identification of possible binding sites for MYC proteins and additionally the NM23-H2 protein itself (the transcription factor PuF for c-myc gene activation) is of importance with respect to possible para- and autoregulatory interactions. A comparison of the promoter sequences of both human nm23 genes revealed no significant sequence homology.
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PMID:Characterization of the human nm23-H2 promoter region and localization of the microsatellite D17S396. 748 60

About half of the patients with follicular lymphoma will develop an aggressive B cell lymphoma with morphological changes in growth pattern and cellular morphology. Changes of the immunophenotype, especially of the expression of immunoglobulin (Ig) have been documented less frequently. Multiple tumor samples of two patients with follicular lymphoma who developed tumor progression, were studied by Southern blot analysis for rearrangements of the Ig genes and the oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene rearrangements, especially of the Ig light-chain genes, and the structure of the t(14;18) breakpoint as assessed by the polymerase chain reaction (PRC) and fine restriction mapping, remained unaltered with time. However, both within the functional Ig heavy-chain allele and around the t(14;18) breakpoint, extensive secondary alterations took place. This indicates clonal evolution rather than the appearance of an independent lymphoma. In the first case with progression from follicular lymphoma to Burkitt's lymphoma 3 years after diagnosis, alterations were especially present 3' of the t(14;18) breakpoint. In the second patient with a change from follicular to diffuse centroblastic lymphoma 4 years after diagnosis, subsequent class switches from IgM to IgG and to defective IgH expression were accompanied by deletion of C mu sequences and a rearrangement of the MYC gene, respectively. Additionally, in both patients alterations in individual restriction sites occurred, which most likely were due to somatic mutations within both the functional IgH and translocated allele. Our data indicate that complex alterations of both the functional and non-functional IgH allele may accompany tumor progression and may erroneously suggest the appearance of independent clones by Southern blot analysis. It remains to be established whether these alterations are causative events or the consequence of genetic instability and clonal evolution.
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PMID:Histological conversion of follicular lymphoma with structural alterations of t(14;18) and immunoglobin genes. 756 20

To study genetic alterations related to the development and/or progression of breast carcinoma, we examined amplification of the ERBB2, INT2, and MYC genes, as well as loss of heterozygosity (LOH) at loci on 11p, 16q, 17p (D17S5 and TP53), 17q (D17S74 and NME1), and 18q by restriction fragment length polymorphism analysis. The subjects were 26 patients with small breast carcinomas (< or = 2 cm) and 88 patients with larger breast carcinomas (2 to < 5 cm). All patients were free of distant metastasis. As tumor diameter increased, the frequency of oncogene amplification and LOH at all loci except D17S5 increased. However, there was no relationship between tumor diameter and amplification of specific oncogenes or allelic loss at specific loci. LOH at D17S5 was detected in 40% of small breast carcinomas (< or = 2 cm) and 43% of larger breast carcinomas (2 to < 5 cm). There was a significant correlation of LOH at D17S5 with INT2 amplification or with LOH on 11p, 16q, and 18q. These findings suggest that LOH at D17S5 may be involved in the early stage of breast carcinoma development, while INT2 amplification and LOH at 11p, 16q, and 18q appear to be genetic alterations that occur with tumor progression. In addition, as lymph node metastases were significantly related to amplification of the ERBB2 and MYC genes, and LOH of the NME1 gene, these genetic alterations may play a role in the mechanism of lymph node metastases.
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PMID:Analysis of genetic alterations related to the development and progression of breast carcinoma. 790 63

To investigate the possibility of collaboration between telomeric deletion on the short arm of chromosome 1 and genetic amplification similar to that described in human neuroblastoma, 122 human primary breast tumors were examined by restriction fragment length polymorphism analysis for loss of heterozygosity on 1p32-pter and for the three most frequently amplified genetic regions in breast carcinomas (MYC and ERBB2 protooncogenes and the chromosomal region 11q13). Allelic losses at one or more loci on the telomeric part of the short arm of chromosome 1 was observed in 57 (47%) of 122 informative tumors. MYC, ERBB2, and the 11q13 region were amplified in 23, 20, and 21% of breast tumors, respectively. A correlation was found between loss of heterozygosity on chromosome 1p32-pter and amplification of the MYC (formerly c-myc) protooncogene (P = 0.003), suggesting that these two genetic events may collaborate during tumor progression in human breast cancer. These results, together with those obtained in human neuroblastoma, suggest that the distal part of the short arm of chromosome 1 harbors an unidentified tumor suppressor gene(s), whose inactivation may be involved in MYC family gene amplification (an example of genetic instability) in tumors of various cellular origins.
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PMID:A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer. 791 73

The classical follicular variant of follicle center lymphoma (FCL-fo) is associated with the chromosomal translocation t(14;18)(q32;q21). However, the sole presence of this translocation is not sufficient for malignant transformation, as demonstrated by experiments in a transgenic mouse model. Most of the secondary changes, which play a central role in tumor development and progression and which are presumed to be of prognostic value, are gains and losses of chromosomal material. We analyzed 28 FCL-fo patients using comparative genomic hybridization (CGH). The most frequent imbalances were gains on chromosomes X, 7, 8, 12, and 18 as well as losses of material on chromosome arm 6q. For chromosomes X, 8, 12, and 18, the CGH data allowed further narrowing of the relevant subregions. In addition, novel high-level DNA amplifications were identified in five instances mapping to chromosome bands 1p36, 6p21, 8q24 (2 patients), and 12q13-14. Previously, such amplifications have been identified very rarely in lymphomas. In the 2 patients with amplifications mapping to chromosomal band 8q24, involvement of the MYC proto-oncogene in the amplification unit was demonstrated by Southern blot analysis. These data provide further entry points for studies to identify genes relevant for tumor progression in FCL-fo.
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PMID:High incidence of chromosomal imbalances and gene amplifications in the classical follicular variant of follicle center lymphoma. 869 64


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