Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A malignant stromal tumor of the testis with an osteosarcoma component and five of its metastases mainly containing osteosarcoma have been analyzed for RB1 and TP53 abnormalities. Whereas in the primary tumor and in some of the metastases loss of heterozygosity could not be detected for RB1 or for the 17p13 region in which TP53 is located, other metastases showed such losses of heterozygosity. By polymerase chain reaction analysis an 18-base pair deletion from exon 5 of the TP53 gene was found in a small proportion of primary tumor cells and in one of the metastases, but not in the other metastases. Therefore, in this case neither RB1 nor TP53 seems to play an essential role in the initiation of osteosarcoma.
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PMID:Analysis of a metastasizing testicular mixed gonadal stromal tumor with osteosarcoma components suggests that a malignant tumor with the histology of osteosarcoma may develop without primary involvement of RB1 and TP53. 142 18

Using the hydroxylamine-osmium tetroxide (HOT) technique, we have identified a constitutional point mutation in the retinoblastoma susceptibility gene (RB1) which segregates with the expression of retinoblastoma in five affected family members. One member developed a second primary tumor, a small-cell lung carcinoma (SCLC), which metastasized to the liver. Analysis of liver tumour DNA revealed homozygosity for the constitutional mutation, a G----A transition at the fifth base of intron 21, resulting in the excision of exon 21 from the mRNA. This is the first demonstration of homozygotization of a constitutional RB mutation in a metastatic second primary tumour and underlines the usefulness of the HOT technique for identification of mutations of the RB1 gene.
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PMID:A familial RB1 mutation detected by the HOT technique is homozygous in a second primary neoplasm. 166 95

Loss of heterozygosity (LOH) at the site of the retinoblastoma (RB1) gene, at 13q14, has been shown to occur in a high proportion of ovarian cancer patients. Based on this, RB1 gene inactivation was studied in primary tumor cells from 15 patients with ovarian cancer. Structural changes as well as expression of the RB1 gene were investigated. One patient had a nondisjunctional deletion at the RB1 locus, and the duplicated remaining allele carried a deletion of exon 21. In another patient, without detectable structural changes of the RB1 gene, no RB protein was detected. Allelic losses at the RB1 locus were observed in 8/13 informative cases (61%). Our results indicate that inactivation of the RB1 gene plays a role in tumor development in a minority of ovarian cancer patients. Another gene(s) on 13q also seem(s) to influence malignant transformation in patients with ovarian cancer.
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PMID:Molecular analysis of the retinoblastoma gene in primary ovarian cancer cells. 807 50

The loss or mutational inactivation of the RB1 tumor suppressor gene has been implicated in the development of a diverse group of human malignancies. However, the contribution of the RB1 gene alteration to human prostatic carcinogenesis has been poorly understood. Thus far, deletion of the promoter sequence and exon 21 from one primary tumor specimen and the alterations found in the cell line DU-145, are the only cases of RB1 mutations reported in human carcinoma of the prostate. This study was designed to determine whether alterations in the structure or expression of the RB1 gene occur in human prostate carcinoma, and to determine the nature of these changes and the frequency with which they occur. One hundred twelve primary prostate tumor tissues and four metastatic lesions were obtained immediately after surgical resection. The RB1 gene was characterized in 68 tumor DNA samples using Southern analysis and the PG3.8M or H3-8 probes. Band profiles were analyzed by scanning densitometry. Sixty-three tumor DNA samples were analyzed for defects in the RB1 promoter using polymerase chain reaction (PCR) and heteroduplex analysis. Alterations in the expression of exons 1-27 were analyzed in 79 primary and four metastatic tumor RNAs using RT-PCR. Three of 68 tumors were identified to have gross rearrangement of the RB1 gene or deletion of one allele. One of four stage D tumor specimens showed truncated RT-PCR products indicating an internal deletion of RB1 transcripts. In all, 14 of 83 (17%) specimens displayed abnormally low levels of RB1 mRNA expression. Furthermore, these alterations of RB1 expression showed a correlation with increasing tumor stage and grade. These results suggest alterations of RB1 mRNA expression occur more frequently in higher stages and grades of prostate cancer and, thus, may be contributing to the malignant progression of a subset of human prostate cancer.
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PMID:Alterations of the retinoblastoma gene in human prostate adenocarcinoma. 883 74

CDKN2 (p16(INK4A)/MTS1) is found to be mutated in a variety of human tumor types. To explore the involvement of CDKN2 in prostate carcinogenesis, alterations of CDKN2 were examined in 116 human prostate tissues and cell lines and xenografts. Markedly reduced expression of CDKN2 mRNA was found in 43% (26 of 60) of untreated primary carcinomas, whereas no alteration was observed in 10 benign prostatic hyperplasias. In 17 matched sets from individual patients, 41% of cancerous tissues in contrast to 6% of noncancerous tissues expressed low levels of CDKN2 mRNA, supporting the role of CDKN2 as a tumor suppressor in prostate cancer. Alteration of CDKN2 was observed in each prostate tumor cell line, including one with a missense mutation, and in one of three xenograft tumor tissues derived from primary carcinomas. Two cell lines (PC-3 and TSU-Pr1) expressed only CDKN2 E1beta transcripts, indicating that the expression of CDKN2 E1alpha and E1beta are under separate control in the prostate. A high level of CDKN2 expression was related to abnormal RB1 in one primary tumor and in the DU145 cell line, which expressed the mutated CDKN2 allele. Analysis of genomic DNA indicated that altered CDKN2 expression in primary carcinomas of the prostate was more frequently due to down-regulation of transcription (five of seven) than deletion of the gene (two of seven). Additionally, CDKN2 mRNA was induced in nonexpressor cell lines by treatment with 5-aza-2'-deoxycytidine. This study demonstrates that alteration of CDKN2 is one of the most frequent genetic abnormalities in prostate cancer and may contribute to prostate carcinogenesis.
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PMID:Frequent alteration of CDKN2 (p16(INK4A)/MTS1) expression in human primary prostate carcinomas. 981 78

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver in Japan. Despite progress in operative techniques and adjuvant therapy, the prognosis of ICC remains very poor. Therefore, it is important to investigate the mechanism of carcinogenesis and progression of ICC. We screened allelic losses at 6 loci, including that of novel tumor-suppressor gene FEZ1 on chromosome 8p, and at 5 microsatellite loci to define the association with tumor-suppressor genes (HNPCC, APC, RB1, p53, DCC) in tumors from 18 unrelated ICC patients by PCR-loss of heterozygosity (LOH) assay and correlated the alterations with clinicopathological parameters. As a result, 61.1% (11 of 18) of patients showed LOH at 1 of the loci at least, and microsatellite instability was observed in 16.7% (3 of 18). At locus D8S258, relatively frequent LOH was detected (17.6%) compared with other loci on chromosome 8p. Among the other 5 chromosomal arms tested, the highest frequency of LOH (23.5%) was observed at D17S153. Fifty percent of cases with the mass-forming + periductal infiltrating type were frequently detected by LOH at D8S258 compared to cases of the mass-forming or intraductal growth type. In conclusion, we show that 1 putative tumor-suppressor gene on 8p22 may relate to progression of ICC and suggest that the p53 tumor-suppressor gene may be associated with carcinogenesis of ICC.
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PMID:Allelic loss in human intrahepatic cholangiocarcinoma: correlation between chromosome 8p22 and tumor progression. 1100 73

In order to assess the role of genetic predisposition in the induction of radiation-induced tumors, we performed statistical analysis on data from the literature and from our own Institute with regard to the age at onset and the latency period of osteosarcoma as the second primary tumor for retinoblastoma with or without subsequent radiotherapy. In retinoblastoma survivors who subsequently developed osteosarcoma, the age at onset of retinoblastoma was young (average of 12 months) in both unilateral and bilateral forms. This suggests that all or almost all of the patients were genetically predisposed by a mutation of one allele of the RB1 gene. For retinoblastoma patients, osteosarcomas occurred 1.2 years earlier inside than outside the radiation field. The latency period between radiotherapy and osteosarcoma onset was 1.3 years shorter inside than outside the radiation field. Interestingly, a bimodal distribution of latency periods was observed for osteosarcomas arising inside, but not outside the radiation field: 40% occurred after a short latency, while the latency of the remaining 60% was comparable to that of osteosarcoma occurring outside the radiation field. This suggests that different mechanisms may be involved in radiocarcinogenesis. A radiation-induced mutation of the second RB1 allele may be the cause of osteosarcomas occurring after a short delay, while other genes may be affected in those occurring after a longer delay.
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PMID:Osteosarcoma following retinoblastoma: age at onset and latency period. 1144 17

In order to identify genes associated with metastasis of ductal pancreatic adenocarcinoma we investigated pancreatic tumor cell lines derived from an orthotopic pancreatic tumor model in SCID mice. Transcriptional profiling (Affymetrix Gene Chip Technology) was performed with cell lines derived from the primary tumor and metastatic lesions such as mesentery, liver and lungs. We scored for genes commonly deregulated in the cell lines derived from the metastatic lesions. Of 7070 genes investigated, 59 (0.83%) were found to be deregulated in the cell lines derived from the metastatic lesions. We grouped these genes into different categories such as transcription, translation, cytoskeleton, cell adhesion, chromosome instability, tumor suppressor genes, enzymes and "others". The most remarkable features of the system are the up-regulation of high mobility group protein HMG-I (Y), twenty-one ribosomal proteins, GAPDH and the laminin receptor in the cell lines derived from the metastatic lesions, whereas tumor suppressor genes such as maspin and RB1 were down-regulated. Inhibition or reconstitution of the activity of these targets are an emerging strategy for inhibition of metastasis in this system.
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PMID:Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasis-associated genes. 1184 76

To account for the accumulation of genomic alterations required for tumor progression, it has been suggested that the genomes of cancer cells are unstable and that this instability results from defective mutators (the "mutator phenotype" theory). To examine the hypothesis that abnormal cell-cycle regulators act as the mutators contributing to genomic instability, the present study, based on primary tumor tissues from 71 patients with breast cancer, was performed to determine whether there was an association between aberrant expression of cell-cycle regulators (cyclin A, cyclin D1, cyclin E, RB1, p21, and p27) and chromosomal instability. Comparative genomic hybridization was used to measure chromosomal changes, reflecting genomic instability in individual tumors, whereas immunohistochemistry was used to detect aberrant expression of cell-cycle regulators. Overexpression of cyclin D1 was found to be significantly correlated with increased chromosomal instability (defined as harboring more than 7 chromosomal changes), with 63% of tumors overexpressing and 27% of tumors not overexpressing, with cyclin D1 showing chromosomal instability (P < 0.05). Interestingly, this relationship was independent of cell outgrowth (as detected by the proliferation marker Ki-67) and was particularly significant in tumors not expressing p27 or in tumors with detectable RB1. These results suggest that cyclin D1 plays an alternative role in the regulation of genomic stability.
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PMID:Aberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related to chromosomal genomic instability. 1200 88

Loss of both RB1 alleles is rate limiting for development of retinoblastoma (RB), but genomic copy number gain or loss may impact oncogene(s) and tumor suppressor genes, facilitating tumor progression. We used quantitative multiplex polymerase chain reaction to profile "hot spot" genomic copy number changes for gain at 1q32.1, 6p22, and MYCN, and loss at 16q22 in 87 primary RB and 7 cell lines. Loss at 16q22 (48%) negatively associated with MYCN gain (18%) (Fisher's exact P = 0.031), gain at 1q32.1 (62%) positively associated with 6p "hot spot" gain (43%) (P = 0.033), and there was a trend for positive association between 1q and MYCN gain (P = 0.095). Cell lines had a higher frequency of MYCN amplification than primary tumors (29% versus 3%; P = 0.043). Novel high-level amplification of 1q32.1 in one primary tumor, confirmed by fluorescence in situ hybridization, strongly supports the presence of oncogene(s) in this region, possibly the mitotic kinesin, KIF14. Gene-specific quantitative multiplex polymerase chain reaction of candidate oncogenes at 1q32.1 (KIF14), 6p22 (E2F3 and DEK), and tumor suppressor genes at 16q22 (CDH11) and 17q21 (NGFR) showed the most common gene gains in RB to be KIF14 in cell lines (80%) and E2F3 in primary tumors (70%). The patterns of gain/loss were qualitatively different in 25 RB compared with 12 primary hepatocellular carcinoma and 12 breast cancer cell lines. Gene specific analysis of one bone marrow metastasis of RB, prechemotherapy and postchemotherapy, showed the typical genomic changes of RB pretreatment, which normalized after chemotherapy.
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PMID:Profiling genomic copy number changes in retinoblastoma beyond loss of RB1. 1709 72


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