Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Fourteen primary human lung tumor DNAs from smokers were analyzed for transforming activity by two DNA transfection assays. Activated protooncogenes were detected in 3 of 11 tumor DNAs by the NIH 3T3 focus assay, whereas activated protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection-nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma, a squamous cell carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found to contain an activated RAF gene. Two unidentified transforming genes were detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain RAS oncogenes. No significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6-kilobase EcoRI alleles of the LMYC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from smokers were found to contain activated protooncogenes. RAS oncogenes appear to play a role in the development of metastases in lung adenocarcinomas.
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PMID:Activated protooncogenes in human lung tumors from smokers. 199 9

Some studies have suggested that the S allele of the MYCL oncogene, which results from an intragenic EcoRI restriction fragment length polymorphism (RFLP), may be associated with cancer susceptibility. In addition, this allele has also been linked to metastases and adverse survival in certain cancers, although studies of lung cancer patients from different populations have yielded controversial results. We studied 108 cases of surgical resected non-small-cell lung cancer (NSCLC) and found no evidence that MYCL genotypes were associated with tumour progression or a worse prognosis. However, the presence of loss of heterozygosity (LOH) at this chromosome 1p32 locus correlated significantly with regional lymph node involvement, as well as advanced TNM stage. These data indicate the existence of a chromosome 1p candidate tumour-suppressor gene(s), possibly in linkage disequilibrium with the EcoRI RFLP in specific populations, which appears to play a role in determining tumour progression in NSCLC. Refined mapping of the critical region of loss should help attempts to identify and clone the candidate gene.
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PMID:MYCL genotypes and loss of heterozygosity in non-small-cell lung cancer. 898 Mar 99

The status of microsatellite markers located on chromosomes 1p36, 3p25, 5q23, 9p22, 10q23, 10q24, 17p13, and 19q12 was used to determine loss of heterozygosity (LOH) in primary giant cell tumors (GCT) of bone in 12 patients. The cases included primary, locally recurrent, and metastatic GCT; three tumors were classified as malignant GCT, based on their morphological features. Microdissection was performed on 24 paraffin-embedded tissue samples. An average of three separate topographic sites were microdissected from each tumor. Case selection in each instance was based on the availability of paired samples of tumor in primary GCTs and their corresponding recurrences, and the presence of normal tissue. The number of cases studied is too small for statistical studies, and thus the analysis is descriptive. All cases were informative for >80% of the markers used. Both primary GCTs and local recurrences and lung metastases displayed LOH of three or more markers, and intratumoral heterogeneity was frequent. Fractional allelic losses (FAL) were not different in recurrent and nonrecurrent GCT. FAL was greatest (>30%) in the metastatic group of GCT. Allelic losses of 1p, 9q, and 19q regions were frequent in all groups. LOH of 17p (in proximity to the p53 locus) and 9p occurred exclusively in the pulmonary metastases from GCT. LOH of 9q and 19q was present in primary as well as recurrent GCTs and in one malignant GCT. Involvement of 1p (including MYCL) and 9q regions has not been previously reported in GCT of bone. The pattern of LOH evident in the 17 markers used in the present study suggests that GCT with malignant features may follow an evolutionary pathway similar to the usual primary GCT of bone.
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PMID:Molecular analysis of primary and recurrent giant cell tumors of bone. 1579 59

Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy. However, it is unclear what, if any, genomic alterations occur as the disease progresses to invasive and metastatic OSCC. This study used genomewide array-CGH in microdissected specimens to map genetic alterations found in primary OSCC and neck lymph node metastases. We used array-based comparative genomic hybridization (array-CGH) to screen genomewide alterations in eight pairs of microdissected tissue samples from primary and metastatic OSCC. In addition, 25 primary and metastatic OSCC tissue pairs were examined with immunohistochemistry for protein expression of the most frequently altered genes. The highest frequencies of gains were detected in LMYC, REL, TERC, PIK3CA, MYB, MDR1, HRAS, GARP, CCND2, FES, HER2, SIS, and SRY. The highest frequencies of losses were detected in p44S10, TIF1, LPL, MTAP, BMI1, EGR2, and MAP2K5. Genomic alterations in TGFbeta2, cellular retinoid-binding protein 1 gene (CRBP1), PIK3CA, HTR1B, HRAS, ERBB3, and STK6 differed significantly between primary OSCC and their metastatic counterparts. Genomic alterations in PRKCZ, ABL1, and FGF4 were significantly different in patients who died compared with those who survived. Immunohistochemistry confirmed high PIK3CA immunoreactivity in primary and metastatic OSCC. Higher FGF4 immunoreactivity in primary OSCC is associated with a worse prognosis. Loss of CRBP1 immunoreactivity is evident in primary and metastatic OSCC. Our study suggests that precise genomic profiling can be useful in determining gene number changes in OSCC. As our understanding of these changes grow, this profiling may become a practical tool for clinical evaluation.
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PMID:Array-comparative genomic hybridization to detect genomewide changes in microdissected primary and metastatic oral squamous cell carcinomas. 1667 65

A 20-year-old man developed a soft tissue mass in his right upper arm and, 3 months later, was referred to our hospital. The tumor cells showed brisk mitotic activity and a large amount of cytoplasmic glycogen was demonstrated with periodic acid Schiff stain. A diagnosis of atypical Ewing sarcoma was made. Chemotherapy according to the VACA protocol, comprising vincristine, actinomycin D, cyclophosphamide and doxorubicin was started. The chemotherapy was effective and a limb salvage procedure was performed by implantation of an autoclaved bone after wide tumor excision. During the postoperative chemotherapy, a local recurrence and multiple metastases developed, and the patient died due to disease progression. Fourteen years later, this tumor sample, preserved in a deep-freeze, was analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the fusion gene. This tumor had an EWS exon 7 to FLI1 exon 6 fusion transcript. Moreover, metaphase and microarray comparative genomic hybridization (CGH) was done to detect chromosomal instabilities. Many gains and losses were noted on metaphase CGH, and MYCL amplification was identified on microarray CGH.
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PMID:Amplification of MYCL in Atypical Ewing Tumor. Analysis of Metaphase and Microarray Comparative Genomic Hybridization. 3139 6