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)

Restriction fragment length polymorphisms at 61 autosomal and 7 X-linked loci were screened for heterozygosity in cell lines derived from 6 independent metastases and autologous B-cells from a patient with melanoma. Segregations resulting in the loss of heterozygosity were detected in the tumor cells at 8 of 16 autosomes with at least 1 informative locus and at the 3 informative X-linked loci. With a single exception, karyotypic abnormalities were not detected in the region of loci where loss of heterozygosity had been detected. Three patterns of loss were identified: unique segregations in cells from a single metastasis; segregation of the same alleles in different subsets of metastases; and identical segregations in all 6 metastases. The monoclonal derivation of the 6 metastases is supported by the inactivation of the same X-chromosome and the presence of identical segregation at loci on chromosomes 9 and X. Analysis of the patterns of segregation in the metastatic tumor cells permitted the development of a genealogy of tumor progression in this patient and the development of a model of tumor progression which describes the accumulation of selectively neutral and advantageous segregations in metastatic tumor cells.
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PMID:Loss of heterozygosity at autosomal and X-linked loci during tumor progression in a patient with melanoma. 288 13

To determine the point at which transformation of the germ cell occurs during meiosis in nonseminomatous testicular cancer, the sex chromosome compositions of 15 cell lines derived from primary tumors or metastases of 12 patients with testicular cancer were analyzed by trypsin G-banding analysis and Y-body staining. The simultaneous existence of both X- and Y-chromosomes in a single cell has been confirmed in 14 cell lines. This suggests that transformation of the cell occurs before the first meiotic division because it is known that segregation of X- and Y-chromosomes occurs during the first meiotic division. An incidental finding was the presence of Barr bodies in some cell lines containing more than one X-chromosome, which is consistent with the known primitive nature of testicular cancer and its ability to differentiate independently from the male host.
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PMID:Cytogenetic evidence for premeiotic transformation of human testicular cancers. 616 59

Twenty prostate tumor specimens, obtained from radical prostatectomies, and two lymph node metastases were examined by classical and molecular cytogenetic methods. A sample from each tumor was analyzed histologically and used for touch preparations. Adjacent samples were used for preparation of single-cell suspensions before cell culture (DirFISH) and for establishing cell cultures, which were subsequently harvested for classical G-banding analysis. Fluorescence in situ hybridization (FISH) was performed on touch preparations, DirFISH, and cells obtained from tissue culture. Biotinylated pericentromeric probes for chromosomes 7 and 17, in addition to a digoxigenin-labeled X-chromosome probe, were used in a dual-color FISH assay. The results indicated that, in uncultured tumor cells, chromosome 17 was lost in 55% of specimens, chromosome 7 was gained in 16% of specimens, and 9% of specimens showed large tetraploid populations. After cell culture, 23% of specimens showed loss of chromosome 17, no specimens showed gain of chromosome 7, and no tetraploid populations were present. This study suggests that loss of chromosome 17 may play an important role in the development of prostate cancer, and that genetic changes observed after selection in vitro may not represent those in the original tumor.
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PMID:Aneusomy of chromosomes 7 and 17 detected by FISH in prostate cancer and the effects of selection in vitro. 753 Apr 85

Simultaneous involvement of the endometrium and the ovary by carcinoma is a familiar problem in the routine practice of surgical pathology. Such cases may be considered either examples of a single primary carcinoma with metastasis or as synchronous primary neoplasms. The distinction between these two possibilities is made based on clinicopathologic observations, and therefore may not be definitive. In the present study, the authors used molecular techniques to analyze the clonal composition of five cases of concurrent adenocarcinomas of the endometrium and ovary that were clinicopathologically diagnosed as synchronous primary tumors. Patterns of X-chromosome inactivation, mutations in the K-ras gene, mutations or allelic loss of the p53 gene, or human papillomavirus detection were identical in both endometrial and ovarian lesions in three of the cases suggesting that those three cases represented single primary tumors with metastases. In both of the other two cases, the patterns of X-chromosome inactivation clearly demonstrated the presence of independent primary tumors. The application of molecular technology may play an important role for the differential diagnosis between synchronous primary carcinomas and a single carcinoma with metastasis.
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PMID:Application of clonal analysis. Differential diagnosis for synchronous primary ovarian and endometrial cancers and metastatic cancer. 860 17

We reported that a murine carcinoma (DEN3) an its six pulmonary metastases (M2, M4C, M4D, M4E, M4F, and M6) exhibited different degrees of radioresistability (In Vitro Cell. Dev. Biol.26:222-228; 1990). While the M2, M4C, M4E, and M4F cultured cells survived up to 2.5 Gy, the cells of DEN3 and M6 tolerated up to 5.0 Gy, and the M4D cells could withstand up to 10.0 Gy of X-irradiation. In the present investigation, the cytogenetic features of these cell lines were examined: (a) to determine the degree of cytogenetic heterogeneity among these cell lines, and (b) to investigate whether any association between the cytogenetic anomaly and the degree of radioresistability could be established. Heterogeneous cytogenetic aberrations were detected in all of the above lines. Karyotype analysis of the M4D and M6 cell lines displayed both numerical and structural abnormalities. The gain and loss of chromosomal copies were observed. Structural aberrations, such as translocation and deletion appeared in both cell lines. However, correlation between the cytogenetic abnormality and the degree of radioresistability was not demonstrated except for a dramatic reduction in one or more copies of the X-chromosome that occurred in 86% and 93% of the M6 and M4D cells, respectively. The results suggest heterogeneous cytogenetic aberrations among these cell lines and a possible association between the loss of X-chromosome and radioresistability of these tumor cells.
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PMID:Cytogenetic analyses of a murine carcinoma cell line and six metastatic derivatives with different degrees of radioresistability. 908 Dec 21

Gastrinomas are neuroendocrine neoplasms that occur sporadically and in patients with multiple endocrine neoplasia type 1 (MEN1). In MEN1, multiple gastrinomas have been shown to arise by independent clonal events (Debelenko, et al., Cancer Res., 57: 2238-2243, 1997). The purpose of the present study was to analyze clonality in 20 sporadic gastrinomas from eight patients in whom the tumor was present in at least two separate sites. A combination of methods was used to assess clonality, including MEN1 gene mutation analysis, loss of heterozygosity analysis of the MEN1 locus, and analysis of X-chromosome inactivation at the human androgen receptor locus (human androgen receptor analysis). In three patients, a somantic MEN1 gene mutation was detected in the tumor. Identical mutations were found in other tumors at different sites within the same patients. Human androgen receptor analysis in three informative patients and loss of heterozygosity analysis in five patients revealed identical clonal patterns in the tumors from multiple sites in each patient. We conclude that sporadic gastrinomas at multiple sites are monoclonal and that MEN1 gene alterations in gastrinomas occur before the development of tumor metastases.
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PMID:Identical clonality of sporadic gastrinomas at multiple sites. 1064 53

The relationship among histological features, cell kinetics, and clonality has not been studied in adrenal medullary hyperplasias (AMHs) and phaeochromocytomas (PCCs). Thirty-four PCCs (23 sporadic and 11 MEN-2A (multiple endocrine neoplasia type 2A)-related tumours, the latter associated with AMH) from females were included in this study. Representative samples were histologically evaluated and microdissected to extract DNA and evaluate the methylation pattern of the androgen receptor alleles. At least two tissue samples (from the peripheral and internal zones in each tumour) were analysed with appropriate tissue controls run in every case. The same areas were selected for MIB-1 staining and in situ end labelling (ISEL). Malignant PCCs were defined by histologically confirmed distant metastases. All monoclonal AMH nodules from the same patient showed the same X-chromosome inactivated. Six sporadic PCCs revealed liver metastases (malignant PCC) and eight additional sporadic PCCs showed periadrenal infiltration (locally invasive PCC). All informative PCCs were monoclonal, except for five locally invasive PCCs and one benign PCC that revealed polyclonal patterns. Those cases also showed a fibroblastic stromal reaction with prominent blood vessels, focal smooth muscle differentiation, and significantly higher MIB-1 (126.8+/-29.9) and ISEL (50.9+/-12.8) indices. Concordant X-chromosome inactivation in nodules from a given patient suggests that MEN-2A AMH is a multifocal monoclonal condition. A subgroup of PCCs characterized by balanced methylation of androgen receptor alleles, high cellular turnover, and stromal proliferation also shows locally invasive features.
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PMID:Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias: histological and kinetic correlates. 1100 99

VIN is thought to be the precursor of some VSCCs because it is monoclonal, frequently occurs contiguously with VSCC and shares similar risk factors with a subgroup of VSCC. There has been no conclusive molecular evidence supporting this assumption. We performed X-chromosome inactivation analysis on 9 cases of lone VIN, 10 cases of VSCC and associated contiguous VIN and 11 cases of VSCC and associated noncontiguous VIN. Eight of the 9 cases of lone VIN appeared to be monoclonal. All 7 informative and monoclonal cases of VIN with contiguous VSCC and 6/9 informative cases of VIN with noncontiguous VSCC showed patterns of X-chromosome inactivation consistent with a common monoclonal origin for both VIN and VSCC. Two of the 9 cases of VIN with noncontiguous VSCC showed X-chromosome inactivation patterns consistent with a separate clonal origin. We performed LOH analysis at 6 chromosomal loci on these samples and 7 cases with lymph node metastases. Identical losses occurred 7 times in VIN and contiguous VSCC (random probability 1.2 x 10(-9)), twice in VIN and noncontiguous VSCC (random probability 1.5 x 10(-3)) and 3 times in VSCC and associated metastases (random probability 1.8 x 10(-5)). Some losses occurring in VSCC did not appear in the contiguous VIN or associated metastases and vice versa. These data provide molecular evidence that VIN is the precursor of VIN-associated VSCC, that multifocal disease may arise via either different clones or a single clone and that continued divergent clonal evolution may occur in vulval neoplasia.
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PMID:Molecular evidence of a common clonal origin and subsequent divergent clonal evolution in vulval intraepithelial neoplasia, vulval squamous cell carcinoma and lymph node metastases. 1199 44

The aim of this study was to examine the prevalence of androgen receptor (AR) amplification in metastases to bone and other sites in patients with hormone-refractory prostate cancer (HRPC) and to compare these findings with those in pretreatment primary tumour samples from the same patients. Tissue from 24 patients with HRPC was available for study, together with 13 primary tumour specimens. AR gene amplification and copy number for X-chromosome were assessed by fluorescence in situ hybridization (FISH) using a SpectrumOrange-labelled probe at locus Xq11-13 for the AR gene and a SpectrumGreen-labelled alpha-satellite probe for the X-chromosome (Vysis, UK, Ltd.). A minimum of 20 nuclei were scored in each of three tumour areas by two independent observers. Samples from 18/24 patients with HRPC (12 bone marrow biopsies, three local tumour recurrences, and three lymph nodes) and nine primary tumour specimens were adequate for FISH analysis. Results were expressed as a mean ratio of AR gene copy number : mean X-chromosome number, with a ratio of greater than 1.5 defined as amplification. AR gene amplification was seen in 9/18 (50%) cases of HRPC and in none of the primary (untreated) tumour specimens (p = 0.0048, Fisher's exact test). For the 12 bone marrow samples, AR gene amplification occurred in 5/12 (38%) cases. Elevated copy number for chromosome X occurred in 3/18 (17%) HRPC and 4/9 (44%) matched primary tumours. This study shows for the first time that AR gene amplification can be demonstrated by FISH in bone metastases from HRPC patients. Because bone marrow biopsies can be obtained from most patients with HRPC, the findings provide a rational basis for the routine selection of patients who may respond more favourably to second-line anti-androgen therapy.
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PMID:Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer. 1223 84

Field cancerization was first described in 1953 as histologically altered epithelium surrounding tumor samples taken from the upper aerodigestive tract. Since then, the term has been used to describe multiple patches of pre-malignant disease, a higher-than-expected prevalence of multiple local second primary tumors, and the presence of synchronous distant tumors within the upper aerodigestive tract. Molecular techniques such as karyotype analysis, microsatellite analysis, p53 mutation screening, and X-chromosome inactivation studies have further refined the relationship among these lesions. While there are differences in the techniques used to identify the clonal origins of the lesions, these studies indicate that there is often lateral clonal spread of pre-malignant or malignant disease, and a significant portion of local second primary tumors are in fact genetically related. Distant second primary tumors found in the esophagus are often not related to concurrent head and neck cancer, whereas synchronous squamous lung tumors with a head and neck primary are often, in fact, metastases, rather than independently arising malignancies. These observations help to explain the high incidence of recurrent disease, despite excision or other therapy--pre-malignant or malignant clones often have the ability to migrate and persist outside of the field of treatment. Therefore, alternative means of prevention or therapy that can affect the entire head and neck region may be of benefit to such patients. Future studies will further refine the relationship among these lesions and perhaps identify key molecular alterations to be used as targets for gene therapy.
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PMID:The molecular biology of mucosal field cancerization of the head and neck. 1453 Mar 4


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