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

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

Restriction length fragment polymorphism of the L-MYC gene was examined in DNAs from lung cancer tissues and normal tissues of 51 Japanese patients with lung cancer. In individual patients, no difference was seen between the restriction length fragments of the two alleles of L-MYC [6-kilobase (kb) and 10-kb fragments in EcoRI digests] in lung cancer tissues and normal tissues. But a striking correlation was found between the restriction length fragment polymorphism pattern of L-MYC and the extent of metastasis, particularly to the lymph nodes at the time of surgery: Patients with only the L band (10 kb) had few lymph node metastatic lesions, whereas patients with either the S band (6 kb) or the S and L bands almost always had lymph node metastatic lesion. A similar correlation was found between the presence of the S band and metastases to other organs. This correlation was particularly marked in cases of adenocarcinoma. These results indicate a clear genetic influence on metastases and a consequent poor prognosis for certain patients of lung cancer; L-MYC restriction length fragment polymorphism is thus shown to be a useful marker for predicting the metastatic potential of human lung cancer.
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PMID:Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs. 289 75

Identification of the genetic alterations that occur in tumors is an important approach to understanding tumorigenesis. We have used comparative genomic hybridization (CGH), a novel molecular cytogenetic method, to identify the gross DNA copy number changes that commonly occur in small cell lung cancer (SCLC). We analyzed ten SCLC tumors (seven primary tumors and three metastases) from eight patients. We found frequent increases in DNA copy number on chromosome arms 5p, 8q, 3q, and Xq and frequent decreases in copy number on chromosome arms 3p, 17p, 5q, 8p, 13q, and 4p. The increase in copy number at 8q24 (MYC) and decreases at 17p13 (TP53), 13q14 (RB), and 3p have previously been identified in SCLC with other methods. Many of the other regions in which we detected common copy number changes have not been reported to be regions of common alteration in SCLC tumors. Comparison of copy number changes between a primary tumor and a metastasis from the same patient showed that they were more closely related to each other than to any of the other tumors. The results of direct CGH analysis of SCLC tumors reported here confirm the existence of copy number changes that we identified previously by using cell lines.
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PMID:Identification of novel regions of altered DNA copy number in small cell lung tumors. 766 37

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 determine the relationship between breast cancer progression and gene amplification, we screened 62 distant metastases and 122 primary breast tumours for the amplification of the proto-oncogenes MYC and ERBB2 and the 11q13 chromosomal region. Surprisingly, solid metastases showed an absence of gene amplification. These results suggest that the amplification of the proto-oncogenes MYC and ERBB2 and the 11q13 chromosomal region seem to be involved mainly in the genesis of the primary breast tumour rather than its progression.
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PMID:Classical gene amplifications in human breast cancer are not associated with distant solid metastases. 931 Feb 46

Race is widely believed to be a factor in the relationship between S allele of L-MYC oncogene and disseminated lung cancer. In particular, the clinical significance of L-MYC genotype was demonstrated in the Japanese while the results for the white US, Australian and Norwegian cohorts were negative. The present study was concerned with distribution of L-MYC oncogene alleles in 43 patients with lung cancer and 77 healthy subjects in Moldova. L and S allele frequency in both groups were nearly identical. However, the SS genotype was registered much more frequently in patients with metastasis (10/28; 36%)(p < 0.05) than in those with localized tumor (0/12). Moreover, overall frequency of S allele was significantly higher in lung cancer patients with node involvement (35/56; 63%)(p < 0.02) than in those with localized tumors (8/24; 33%)(p < 0.02). Finally, a significant correlation was found between S allele occurrence and distant metastases (M1: 19/28; 68%; M0:26/58; 45%)(p < 0.05). Similar data were reported in Russia. (ABSTRACT TRUNCATED)
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PMID:[S allele of the L-myc oncogene is associated with lung cancer metastases in patients from Moldova]. 957 28

Prostate cancer development and progression is driven by the accumulation of genetic changes, the nature of which remains incompletely understood To facilitate high-throughput analysis of molecular events taking place in primary, recurrent, and metastat prostate cancer, we constructed a tissue microarray containing small 0.6-mm cylindrical samples acquired from 371 formalin-fixed blocks, including benign prostatic hyperplasia (n = 32) and primary tumors (n = 223), as well as both locally recurrent tumors (n = 54) and metastases (n = 62) from patients with hormone-refractory disease. Fluorescence in situ hybridization (FISH) was applied to the analysis of consecutive tissue microarray sections with probes for five different genes. High-level (> or =3X) amplifications were very rare (<2%) in primary prostate cancers However, in metastases from patients with hormone-refractory disease, amplification of the androgen receptor gene was seen in 22%, MYC in 11%, and Cyclin-D1 in 5% of the cases. In specimens from locally recurrent tumors, the corresponding percentages were 23, 4, and 8%. ERBB2 and NMYC amplifications were never detected at any stage of prostate cancer progression. In conclusion, FISH to tissue microarray sections enables high-throughput analysis of genetic alterations contributing to cancer development and progression. Our results implicate a role for amplification of androgen receptor in hormonal therapy failure and that of MYC in the metastatic progression of human prostate cancer.
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PMID:Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. 1002 66

We analyzed eight samples of xenografted human pancreatic tumors and two metastases developed in mice by comparative genomic hybridization (CGH). The most recurrent changes were: gains on chromosomes 8 (8q24-qter; 7/8 cases), 15 (15q25-q26; 6/8 cases), 16 (16p in 6/8 cases; 16q in 5/8 cases), 20 (20q; 6/8 cases), and 19 (19q; 5/8 cases); and losses on chromosomes 18 (18q21; 6/8 cases), 6 (6q16-q21 and 6q24-qter; 5/8 cases each), and 9 (9p23-pter; 5/8 cases). The two metastases maintained the aberrations of the original pancreatic tumor plus gain of 11q12-q13 and 22q. Loss of heterozygosity analysis was carried out for 10p14-pter, a region that was lost in 3/8 samples. All of them presented allelic imbalance for all the informative loci. Fluorescence in situ hybridization and Southern analysis were performed to test some candidate oncogenes in 8q24 (MYC) and 15q25-qter (IGF1R and FES). Two of seven tumors showed high-level amplification of MYC relative to the centromere (> 3-fold), another two tumors had low-level amplification (1.5- to 3.0-fold), and one displayed 5.5 MYC signals/cell. In relation to the FES gene, low-level amplification was found in three tumors. Southern analysis showed five cases with a low-level amplification of IGF1R. Our data suggest that either few extra gene copies may be enough for cancer progression or other genes located in these regions are responsible for the amplifications found by CGH.
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PMID:DNA copy number changes and evaluation of MYC, IGF1R, and FES amplification in xenografts of pancreatic adenocarcinoma. 1064 Jan 45

To identify the genetic prognostic markers for breast cancer, we analyzed loss of heterozygosity (LOH) at 11p, 16q, 17p, 17q, and 18q, as well as amplification of the ERBB2, INT2, and MYC genes, in 131 patients with breast carcinoma, 49 of whom had lymph node involvement, but none of whom had distant metastases. Among the several chromosome arms tested, LOH at 17q was correlated with lymph node metastasis. Amplification of the ERBB2, MYC, and INT2 genes was found more frequently in tumors from patients with lymph node metastases than in tumors from those without lymph node metastases. Univariate analysis demonstrated that LOH at 17q and INT2 amplification were factors influencing disease-free survival (DFS). A multivariate analysis was performed on 89 tumors that were able to be evaluated for both LOH at 17q and INT2 amplification, and the results showed that patients who had tumors with these genetic changes were more likely to have a poor prognosis. The findings of this study suggest that investigating genetic changes, in addition to conventional clinicopathologic factors, may contribute to defining groups of breast cancer patients with differences in prognosis.
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PMID:Identification of high-risk breast cancer patients from genetic changes of their tumors. 1088 62

In most of the studies about molecular alterations in squamous cell carcinomas of the head and neck there is not distinction between the different subsites of this area. The objective of this study is to describe the molecular alterations in squamous cell carcinomas of the oropharynx. Twenty-nine oropharyngeal carcinomas, with a minimum follow-up of 36 months, were studied. The molecular alterations analyzed were: the amplification of 11q13 region (in the 29 cases), and the MYC and ERBB1 oncogenes (in 22 cases); the integration of Human Papillomavirus (HPV) types 6b and 16 (in 22 cases); the loss of heterozygosity (LOH) of p53 and N-acetyltransferase-2 (NAT2) gene (in 12 and 13 informative cases, respectively); and the cellular DNA content (in 13 cases). The most frequent alterations found were the LOH at p53 (67%), and NAT2 (54%) locus, followed by 11q13 amplification (49%). ERBB1 amplification was found in 14% of the cases, and MYC amplification only in one (5%). Integration of the HPV was found in 23% of the cases. Nine (69%) of the 13 analyzed cases were aneuploid. The only alteration with a prognostic significance was 11q13 amplification that showed a tendency to be associated with a higher frequency of nodal metastases and tumor recurrence.
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PMID:[Molecular changes in epidermoid carcinoma of the oropharynx]. 1126 75


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