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)

Previous reports have suggested that heterozygotes for ataxia-telangiectasia (A-T) have an increased risk of cancer, in particular breast cancer. The ATM gene, responsible for A-T, was recently cloned. Loss of heterozygosity (LOH) in the chromosome band 11q23, where the ATM gene is located, has been reported in several types of tumours including breast carcinomas. Whether the ATM gene is the target, and the sole target, for the LOH seen in this region is not yet known. In this study, 169 primary breast carcinomas and 10 metastases were examined for allelic imbalance (AI) using 10 microsatellite markers mapping to 11q23.1. Nine of the markers reside within a 10 Mb region surrounding the ATM gene, whereas the tenth locus, APOC-3, is located more than 12 Mb telomeric from this region. The highest frequencies of alteration were found for APOC-3 (45%), and for two markers located approximately 200 and 900 kb telomeric from ATM, D11S1294 (44%) and D11S1818 (44%). The marker located within the ATM gene, D11S2179, was altered in 37% of the informative tumours. The present deletion map indicates that three distinct regions at 11q23.1 may be involved in breast cancer development; one between the markers D11S1294 and D11S1818, a second close to APOC-3, and a third that is possibly the ATM-gene itself.
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PMID:Loss of heterozygosity at 11q23.1 in breast carcinomas: indication for involvement of a gene distal and close to ATM. 907 70

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto the ends of chromosomes, thereby preventing the replication-dependent shortening of these ends. Telomerase activity is detected in a wide range of cancers of various tissues, and its expression may be a critical step in tumor progression. The telomeric repeat amplification protocol was used to compare telomerase activity in breast cancers with and without lymph node metastases, as well as in fibroadenomas and normal breast tissue. Expression of telomerase was detected in 22 (79%) of 28 primary breast cancers, which included 16 (73%) of 22 cancers positive and 6 (100%) of 6 cancers negative for axillary lymph node metastases. It was detected in 1 (11%) of 9 fibroadenomas but was negative in 13 normal breast tissues. There was no statistical difference in expression of telomerase between axillary node-negative primary breast cancers and similar tumors with nodal metastasis (P = .289). Further, no statistical association was found between telomerase activity and tumor size (P = .679) or hormonal status (P = .178). The difference in telomerase activity among breast cancers vs fibroadenomas and normal breast tissues, however, was statistically significant (P < .001). Although normal breast tissue does not express telomerase, both node-positive and node-negative breast cancers express telomerase. The possible significance of telomerase expression in fibroadenomas remains open to further investigation.
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PMID:Telomerase expression in human breast cancer with and without lymph node metastases. 912 66

The telomeric repeat amplification protocol was used to detect expression of telomerase in primary intracranial tumors. Expression was confined to high-grade variants; 10 of 19 glioblastoma multiforme tumors and 5 of 5 primitive neuroectodermal tumors showed telomerase activity. Two of 8 anaplastic gliomas (1 anaplastic oligodendroglioma and 1 anaplastic oligoastrocytoma) were positive for telomerase. Of 16 meningiomas tested, only the 2 atypical variants were positive for telomerase. Two hemangiopericytomas of the central nervous system also showed expression of telomerase. Twenty-two pituitary adenomas (including 6 invasive variants), 2 low-grade gliomas, 2 ependymomas, and 8 nonneoplastic brain specimens were negative. It was concluded that expression of telomerase is found in most glioblastoma multiforme tumors; primitive neuroectodermal tumors appeared to be more uniformly positive. Expression of telomerase in atypical variants of meningioma and hemangiopericytomas of the central nervous system correlated with the potential for aggressive local growth and metastases. Despite the invasive tendency of some pituitary adenomas, telomerase was not detected in these tumors, which suggests that other pathways account for their aggressive behavior.
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PMID:Differential telomerase expression in human primary intracranial tumors. 912 67

The ends of vertebrate chromosome are composed of large tracts of a repeated sequence, TTAGGG, which are known as telomeres. Normal somatic cells progressively lose telomeric repeats with each successive cell division due to incomplete replication. Immortal and cancer cells compensate for telomeric loss by expressing the enzyme telomerase, an RNA-dependent DNA polymerase that maintains telomere length. Telomerase activity has been detected in almost 90% of all human cancers. Telomerase activity is generally absent in normal somatic tissues but is detected in adult testes, activated lymphocytes, and lower levels are expressed in proliferative cells of renewal tissues. Telomerase activity is downregulated in cells that exit the cell cycle via either terminal differentiation or (reversible) quiescence. Inhibition of telomerase activity in tumour cells may provide an effective way to treat cancer by potentially reducing the recurrence of tumours due to occult micro-metastases. An understanding of the pathways involved in telomerase regulation will be important for determining the most practical means of inhibiting its activity.
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PMID:Multiple pathways for the regulation of telomerase activity. 928 14

Only limited data are available on chromosomes specifically involved in the multistep tumorigenesis of prostate cancer. To investigate the cytogenetic status at different stages of prostatic tumor development, we have applied interphase in situ hybridization (ISH) with a set of (peri) centromeric DNA probes--specific for chromosomes 1, 7, 8, and Y--to routinely processed tissue sections of prostatic specimens from 75 different individuals. Our panel consisted of: 16 normal/benign prostatic hyperplasia specimens; 23 primary, localized, prostatic tumors (N0M0 stage); 20 regional lymph node metastases (M0 stage); and 16 distant metastases. Numerical aberrations of at least one chromosome were not observed in normal/benign prostatic hyperplasia cases, but were present in localized tumors (39%), regional lymph node metastases (40%), and distant metastases (69%). Within the different pTNM groups, we observed the following aberrations (listed, within each series, in decreasing order of frequency): -Y, +8, -8, +7 in primary tumors; +8, +7, -Y, +Y, -8 in regional lymph node metastases; and +8, +7, +1, -Y, -8 in distant metastases. In primary tumors, the number of aberrant cases increased significantly with local tumor stage (p < 0.05). A significant increase in gain of chromosome 8 was also observed (p < 0.02). Gain of chromosome 7 and/or 8 showed a significant increase with progression of local tumor stage (p < 0.02). Specific involvement of chromosome 8 was seen in bone metastases, but not in hematogenous metastases to other sites (p = 0.02). Comparative genomic hybridization analysis of these bone metastases disclosed centromere 8 gains as amplifications of the (whole) 8q arm, whereas centromeric loss appeared to be due to loss of 8p sequences. With progression toward metastatic disease, an accumulation of genetic changes was seen as exemplified by gain of chromosome 1, which was solely observed in distant metastases. With tumor progression, gain of chromosomes 7 and/or 8 significantly increased (p = 0.03), whereas the number of cases with aberrations of the Y chromosome did not change. Furthermore, ploidy status determined by ISH revealed a significant increase in the number of aneuploid cases along with advancement of pTNM stage (p = 0.04). Collectively, the data strongly suggest that: (a) gain of chromosome 7 and/or 8 sequences is implicated in prostatic tumor progression; (b) gain of chromosome 8 sequences is related to local tumor growth; (c) overrepresentation of 8q sequences, most likely by isochromosome 8q formation, is involved in metastatic spread to the bone; and (d) changes in the centromeric copy number, as detected by interphase ISH, might in some cases represent structural alterations, such as an isochromosome.
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PMID:Interphase cytogenetics of prostatic tumor progression: specific chromosomal abnormalities are involved in metastasis to the bone. 938 87

Telomerase has been reported to be activated in most immortal cells and human cancers. In the present study, we assessed the correlation between telomerase activity and cellular DNA ploidy level in gastric cancer. Telomerase activity was determined semiquantitatively using the telomeric repeat amplification protocol assay, a polymerase-chain-reaction-based assay, in surgical specimens of primary tumors obtained from 36 patients with gastric cancer. No correlation was observed between telomerase activity and the proliferating cell nuclear antigen labeling index. In contrast, a positive linear correlation was observed between telomerase activity and the DNA index (r = 0.59; p < 0.01). Tumor cells with aneuploid patterns showed higher telomerase activity than those with diploid patterns (27.6+/-5.8 vs. 5.8+/-1.1%; p < 0.01). Telomerase activity of tumors with liver metastases was significantly higher than activity of those without metastases (34.5+/-16.6 vs. 11.8+/-2.4; p < 0.05). There was a trend toward a lower survival rate in 9 patients with a telomerase activity of 20% or higher compared to 27 patients with telomerase activity lower than 20%. These results suggest that the telomerase activity of gastric cancer tissue may reflect the malignant potential of the tumor.
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PMID:Correlation between telomerase activity and DNA ploidy in gastric cancer. 956 59

At present, little information is available on tumor and stage-specific chromosomal aberrations in malignant melanoma. Therefore, we applied fluorescence in situ hybridization on isolated interphase cells from paraffin sections of 25 cases of malignant melanomas, comprising 17 primary tumors (PTs) and 8 metastases (MTs) in various anatomical sites. We used centromeric probes for chromosomes 1, 7, 9, 10, 11, 12, 15, 17, 18, X, and Y and a midisatellite probe localized in 1p36. Four of the PTs and 5 of the MTs showed polyploidy for all applied probes. The most frequent type of numerical aberration was an overrepresentation of chromosomes 1 (3 PTs, 5 MTs) and 7 (3 PTs, 1 MT), and an underrepresentation of chromosomes 9 (3 PTs) and 10 (6 PTs, 5 MTs). The Y chromosome was lost in all male tumors. In addition, we observed monosomy 11, 12, 15, 17 or 18, and trisomy 12 or 17. Only 1 PT showed no aberrations for any applied DNA probe. A deletion in the near-telomeric region of 1p36 was found surprisingly often (9 PTs, 7 MTs). Our results suggest that the loss of gene(s) in this region is an important event in the pathogenesis of malignant melanoma of the skin.
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PMID:An increased frequency of numerical chromosomal abnormalities and 1p36 deletions in isolated cells from paraffin sections of malignant melanomas by means of interphase cytogenetics. 966 9

Only limited data are available on chromosomes specifically involved in prostatic tumour progression. This study has evaluated the cytogenetic status of primary prostatic carcinomas, local tumour recurrences, and distant metastases, representing different time points in prostatic tumour progression. Interphase in situ hybridization (ISH) was applied with a set of (peri) centromeric DNA probes, specific for chromosomes 1, 7, 8 and Y, to routinely processed tissue sections of 73 tumour specimens from 32 patients. Longitudinal evaluation was possible in 11 cases with local recurrence and nine cases with distant metastases. The remaining 12 patients showed no evidence of local recurrence or distant metastasis after radical prostatectomy on follow-up (mean 60.5 months) and served as a reference. Numerical aberrations of at least one chromosome were found in 27 per cent of the local recurrences and 56 per cent of the distant metastases. In decreasing order of frequency, +8, +7, and -Y were observed in the recurrences and +8, +7, -Y, and +1 in the distant metastases. Evaluation of the corresponding primary tumour tissue of the recurrence group showed numerical aberrations in 45 per cent of cases. The aberrations found were, in decreasing order of frequency, -Y, +7, and +8. In the concomitant primary tumour tissue of the distant metastasis group, numerical aberrations were detected in 67 per cent of cases. The aberrations most frequently encountered were +8, -Y, followed by +7. In four cases, a concordance was found between the primary tumour and its recurrence or distant metastasis. Discrepancies might have been caused by cytogenetic heterogeneity. Comparison of the primary tumour tissue of the reference, the recurrence, and the distant metastasis groups showed a significant increase for the percentage of cases with numerical aberrations (Ptrend = 0.02). Likewise, a trend was seen for gain of chromosome 7 and/or 8 (Ptrend < 0.05). The number of DNA aneuploid tumours also increased in these different groups (Ptrend = 0.03). These data suggest that cancers which recur in time display an intermediate position between tumours of disease-free patients and metastatic cancers.
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PMID:Longitudinal evaluation of cytogenetic aberrations in prostatic cancer: tumours that recur in time display an intermediate genetic status between non-persistent and metastatic tumours. 977 81

Novel oncogene mutation detection techniques have demonstrated that standard histopathological examination may fail to detect clinically significant metastatic cancer cells. Recently, telomerase activity has been detected in most immortal cell lines and human tumors, potentially providing a novel diagnostic marker. We compared standard histopathological examination with the telomeric repeat amplification protocol assay and either a p53 plaque hybridization or a K-ras mutation ligation assay in the lymph nodes of 12 patents with surgically resectable non-small cell lung cancer. Telomerase activity was detected in 10 of 10 (100%) evaluable tumors. Eight of 9 (89%) histopathologically positive lymph nodes were telomerase positive, and 26 of 48 (54%) histopathologically negative lymph nodes were telomerase positive. In comparison, oligonucleotide plaque hybridization detected metastases in all 3 histopathologically positive nodes and in 3 of 27 histopathologically negative nodes. Similarly, the K-ras mutation ligation assay detected metastases in all 6 histopathologically positive lymph nodes examined and in 1 of 21 histopathologically negative lymph nodes. Thus, most of the "positive" nodes by telomerase assay did not harbor occult neoplastic cells that shared the same genetic alteration as the primary tumor. The high rate of false positives associated with the telomeric repeat amplification protocol assay limits its role in staging lymph nodes in patients with non-small cell lung cancer.
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PMID:Comparison of oncogene mutation detection and telomerase activity for the molecular staging of non-small cell lung cancer. 981 1

Recent evidence indicates that telomerase activity may be necessary for cell immortality, which is required for the sustained and indefinite growth of most malignant cells. We analyzed telomerase activity in gastric and colorectal cancers and in gastric and colorectal precancerous lesions to determine whether malignant progression depends on the activation of telomerase and at what stage of carcinogenesis cells have detectable telomerase activity. Telomerase activity was measured by the telomeric repeat amplification protocol assay and was detected in 17 (85%) of 20 primary gastric carcinoma tissues and in 19 (95%) of 20 primary colorectal carcinomas, regardless of tumor staging and histological types. All nodal metastases, peritoneal metastases, and a recurrent gastric cancer tumor were positive. All cell lines established from gastric and colorectal cancers contained telomerase activity. In precancerous lesions, 10 (100%) of 10 colorectal tubular adenomas were telomerase positive, in addition to 3 (23%) of 13 gastric intestinal metaplasias and 1 (50%) of 2 gastric adenomas, whereas the corresponding gastric normal mucosas as well as colorectal mucosas were negative. These results indicate overall that reactivation of telomerase may occur at an early stage of carcinogenesis and may correlate well with malignant progression of gastric cancer. Telomerase activity thus may serve as a powerful additional tool for cancer diagnosis.
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PMID:Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. 981 18


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