Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis and interrelationships of neuroendocrine lung carcinomas are not well understood. Tissue macro-arrays prepared from surgical resection specimens from 35 patients with typical carcinoid (TC), six with atypical carcinoid (AC), 13 with large cell neuroendocrine carcinoma (LCNEC), and 15 with small cell lung carcinoma (SCLC) were investigated by fluorescence in situ hybridization (FISH) and immunohistochemistry. Hybridizations with locus-specific DNA probes demonstrated a high incidence of deletion for the tumour suppressor genes p53 and retinoblastoma (Rb), and for the oncogene cyclin D1, comparable in all carcinoma types. Similarly, an increase of DNA copy number for the Her-2/neu and c-myc oncogenes was noted in all neoplasms. A more detailed quantitative analysis of the results, however, demonstrated increasing numbers of cells harbouring these genomic alterations, from low-grade TC to highly malignant SCLC, with the exception of cyclin D1 deletion. Mutations of the p53 and Rb genes, as assayed by immunohistochemical studies, were observed at high incidence in high-grade carcinomas, compared with a low incidence in the low-grade carcinomas. Conversely, in all carcinoma types, neither membrane-bound Her-2/neu nor nuclear cyclin D1 was detected. It is concluded that structural genomic alterations are frequent in neuroendocrine lung carcinomas and that their occurrence may be underestimated by immunohistochemical studies alone. The quantitative expansion of the Rb, p53, c-myc, and Her-2/neu alterations towards high-grade carcinomas suggests common pathogenetic mechanisms in the spectrum of these neoplasms.
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PMID:Quantitative expansion of structural genomic alterations in the spectrum of neuroendocrine lung carcinomas. 1192 Jul 36

In small cell lung cancer (SCLC), hypermethylation of the tumour suppressor Ras association domain family 1A (RASSF1A) is frequent. It is associated with SV40 polyomaviral infection in other tumours. Merkel cell polyomavirus (MCPyV) infection has been reported in Merkel cell carcinoma (MCC), a neuroendocrine carcinoma with biological similarity to SCLC. In our study, we investigated polyomavirus infection (SV40 and MCPyV) and promoter hypermethylation of the tumour suppressors RASSF1A and p16 in 18 SCLCs (14 primaries and 4 regional lymph node metastases) and 18 blood control samples. MCPyV was found in 39% (7 of 18) of the tumour tissues but not observed in controls. SV40 was not observed in the tumour tissue. RASSF1A promoter hypermethylation (94%; 17 of 18) was more frequent compared to p16 methylation (56%, 10 of 18). We found no significant correlation between RASSF1A or p16 promoter hypermethylation and infection with the investigated polyoma viruses. Our results show a high frequency of hypermethylation of the RASSF1A promoter and occurrence of MCPyV infection in the tumour tissue of SCLC. These events may contribute to the pathogenesis of SCLC.
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PMID:Frequent hypermethylation of RASSF1A tumour suppressor gene promoter and presence of Merkel cell polyomavirus in small cell lung cancer. 1947 31