Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we examined the VDJ region of the immunoglobulin heavy chain (IgH) gene in intravascular malignant lymphomatosis (IML). The VDJ regions were amplified using the polymerase chain reaction (PCR) with consensus primers of the V and J regions of the IgH gene. Specimens from all the IML cases produced a monoclonal band. Specimens from metastatic carcinomas, brain tumors and normal tissues produced no monoclonal amplification. By cloning and sequencing the amplified VDJ regions, we have determined nucleotide sequences of rearranged regions of the IgH genes. In addition, we also examined tumor suppressor genes. The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis revealed no abnormal migration in exons 5 to 8 of the p53 gene, exon 2 of the p16 gene and exon 2 of the p21 gene. These findings suggested that mutation of p53, p16 and p21 genes is rarely related with the tumorigenesis of IML. The presence of Epstein-Barr virus (EBV) was also analyzed using PCR. EBV DNA was detected in one of five IML specimens. This result indicates that IML may be associated with EBV.
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PMID:[Molecular genetic analysis of intravascular malignant lymphomatosis cells]. 875 34

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small tumors predominantly on the face. To map the causative gene, we performed linkage analysis with microsatellite markers in three American families. We found a significant linkage of a gene for MFT to chromosome 9p2l. The maximum combined lod score was 3.31 at D9S171 at theta = 0. The disease locus was defined to a 4-cM region between IFNA and D9S126. Because several tumor suppressor genes including p16 and p15 have been mapped to this region, the gene for MFT may also be a tumor suppressor.
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PMID:The gene for multiple familial trichoepithelioma maps to chromosome 9p21. 875 37

The tumor suppressor p16INK4A with eight N-terminal amino acids deleted (p16/delta 1-8) was expressed in Escherichia coli without any fusion artifacts and purified. The integrity of p16/delta 1-8 was confirmed by mass spectrometry, and its activity was demonstrated by in vitro cdk4 inhibition assay. Various physical methods were used to characterize the molecular and structural properties of p16/delta 1-8. The protein was found to oligomerize in vitro, as demonstrated by gel electrophoresis, mass spectrometry, and NMR. Various approaches, including changes of concentration and pH, additions of salts, detergents, and various organic solvents, and construction of a C-terminal deletion mutant and a cysteine mutant were used to try to reduce the extent of oligomerization. Only decreasing the protein concentration was found to reduce oligomerization. The affinity between p16 molecules in vivo was demonstrated by the yeast two-hybrid system. The protein was found to be very unstable on the basis of urea- and guanidinium chloride-induced denaturation studies monitored by NMR and CD, respectively. Despite these unfavorable properties, total NMR assignments were accomplished with uniform 13C and 15N isotope labeling. All multidimensional NMR experiments were performed at a very low concentration of 0.2 mM. The secondary structure was then determined from the NMR data. The results of NMR and CD studies indicate that the protein is highly alpha-helical, and the ankyrin repeat sequences show helix-turn-helix structures. This is the first structural information obtained for the important motif of ankyrin repeats. Overall, p16/delta 1-8 appears to be conformationally flexible. In order to understand the structural basis of the functional changes for some mutants existing in tumor cells, several missense mutants of p16/delta 1-8 were constructed. Four of them were expressed at high levels and purified. The molecular and structural properties of these mutants were analyzed by CD and NMR and compared with the corresponding properties of wild-type p16/delta 1-8. The results suggest that the functional changes in P114L and G101W are likely to be related to global conformational changes. In addition, we have demonstrated that the tendency of aggregation increases significantly by a single D84H mutation.
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PMID:Tumor suppressor p16INK4A: structural characterization of wild-type and mutant proteins by NMR and circular dichroism. 875 27

Precise mapping of DNA methylation patterns in CpG islands has become essential for understanding diverse biological processes such as the regulation of imprinted genes, X chromosome inactivation, and tumor suppressor gene silencing in human cancer. We describe a new method, MSP (methylation-specific PCR), which can rapidly assess the methylation status of virtually any group of CpG sites within a CpG island, independent of the use of methylation-sensitive restriction enzymes. This assay entails initial modification of DNA by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequent amplification with primers specific for methylated versus unmethylated DNA. MSP requires only small quantities of DNA, is sensitive to 0.1% methylated alleles of a given CpG island locus, and can be performed on DNA extracted from paraffin-embedded samples. MSP eliminates the false positive results inherent to previous PCR-based approaches which relied on differential restriction enzyme cleavage to distinguish methylated from unmethylated DNA. In this study, we demonstrate the use of MSP to identify promoter region hypermethylation changes associated with transcriptional inactivation in four important tumor suppressor genes (p16, p15, E-cadherin, and von Hippel-Lindau) in human cancer.
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PMID:Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. 879 Apr 15

The tumor suppressor gene encoding the cyclin-dependent kinase inhibitor p16 has, remarkably, been found to encode a second protein, p19, with a distinct sequence translated from an alternative reading frame; like p16, p19 can block the cell cycle in G1 phase.
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PMID:Two tracks but one race? Cancer genetics. 880 69

The p16 (CDKN2/cyclin-dependent kinase-4 inhibitor/multiple tumor suppressor-1) gene is frequently altered in cell lines and some types of cancers. To assess whether alterations of this gene are important in the pathogenesis of cervical cancer, we examined 41 primary tumors and 8 cell lines, using Southern blot and polymerase chain reaction-single strand conformation polymorphism analyses. We did not detect any deletions or mutations, which indicates that inactivation of the p16CDKN2 gene is not critical in the tumorigenesis of cervical cancer or in establishment of cervical cancer cell lines.
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PMID:p16 (CDKN2/cyclin-dependent kinase-4 inhibitor/multiple tumor suppressor-1) gene is not altered in uterine cervical carcinomas or cell lines. 882 52

While most authors currently classify dural-based hemangiopericytoma (HPC) as a distinct entity rather than as a subtype of meningioma, the histogenesis of HPC has long been debated. We have recently shown that meningiomas contain frequent mutations of the neurofibromatosis 2 gene, while HPCs do not, suggesting that HPC is genetically distinct from meningioma. In the present study, we evaluated a series of 31 dural HPCs (including 3 pairs of primary and recurrent tumor) and 26 meningiomas for alterations in the cell-cycle regulatory genes CDKN2/p16 and p53. Homozygous deletions of the CDKN2/p16 gene were detected using a comparative multiplex polymerase chain reaction assay in 7 of 28 primary HPCs (25%), but in only one of 26 meningiomas (P = 0.03). Among the HPCs with recurrence, 1 pair of 3 had a homozygous CDKN2/p16 deletion. The 1 meningioma with a CDKN2/p16 deletion was a meningothelial meningioma, without atypical or malignant features. Single-strand conformational polymorphism analysis of all three exons of CDKN2/p16 and exons 5-8 of p53 revealed no mutations in either HPCs or meningiomas. These results illustrate that homozygous deletions of CDKN2/p16 occur in HPCs and suggest that alterations of the p16-mediated cell-cycle regulatory pathway may underlie the formation or progression of some HPCs. The data also provide further genetic evidence that HPC is not a subtype of meningioma.
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PMID:Homozygous deletions of the CDKN2/p16 gene in dural hemangiopericytomas. 883 33

Exons 1-3 of the p16/CDKN2 gene, exons 4-9 of the p53 gene and exons 1 and 2 of H-, K- and N-ras genes were screened for mutations by a combination of immunohistochemistry and single-strand conformational polymorphism (SSCP) analyses of polymerase chain reaction products from human surgical samples of both frank oral squamous cell carcinomas and premalignant lesions. The samples included 20 squamous cell carcinomas, 10 epithelial dysplasias and 10 epithelial hyperplasias. No identifiable gene mutations were detected in any of the dysplasias or hyperplasias, while 2 (10%) deletions and 2 (10%) mutations of p16/CDKN2, along with 5 (25%) p53 mutations were found in the advanced carcinomas, yielding characteristic p16/ CDKN2 and p53 changes. A mutation in the K-ras gene was found in single carcinoma and dysplastic samples. From the data, it can be argued that p16/CDKN2 and p53 mutations are relatively late occurrences in human oral tumorigenesis and that genetic alterations of the ras genes may not play a significant role in squamous neoplasia.
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PMID:Alterations of p16/CDKN2, p53 and ras genes in oral squamous cell carcinomas and premalignant lesions. 883 20

p16/CDKN2/MTS1, a putative tumor suppressor gene, located in the chromosome 9p21 region was cloned in 1994. This gene encodes a protein that binds to and inhibits cyclin-dependent kinase 4 (CDK4), and plays a role in cell cycle regulation. p16 gene has been reported to be homozygously deleted in a variety of human tumors. Using PCR-based assays for exons 2 and 3 of p16 gene, we found homozygous deletions in 15 (48%) of 31 non-small cell lung cancer (NSCLC) cell lines. In contrast, none of 11 small cell lung cancer (SCLC) cell lines had p16 deletions (p = 0.012). Taken together with results previously reported, our data indicate that p16 gene is more frequently deleted in NSCLC than in SCLC. Although the incidence of p16 abnormalities in NSCLC surgical specimens is inconclusive, recent reports suggest that p16 abnormalities are well correlated with tumor dissemination. The role of p16 gene in pathogenesis of lung cancer remains to be elucidated.
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PMID:[p16/CDKN2/MTS1 gene abnormality in lung cancer]. 883 5

Rearrangement and overexpression of the PRAD1/cyclin D1 oncogene, a cell cycle regulator, have been implicated in the pathogenesis of a subset of parathyroid adenomas. Recently, two cell cycle regulators that inhibit the cyclin D1-associated kinases cdk4 and cdk6 have been identified: p16 and p15, the products of the INK4A (also known as CDKN2, MTS1) and INK4B (also known as MTS2) putative tumor suppressor genes located on 9p21. Because inactivation of the p16 or p15 genes might be expected to result in oncogenic consequences similar to those from cyclin D1 overexpression, we examined 25 parathyroid adenomas for 1) allelic loss of polymorphic DNA loci on chromosome arm 9p, 2) homozygous deletions of the p16 and p15 genes by Southern blot analysis, and 3) mutations of the p16 and p15 genes by single strand conformational polymorphism analysis. Heterozygous allelic loss at 9p was observed in 4 of 25 adenomas (16%); their smallest shared region of deletion was 9p21-pter, which includes both the p16 and p15 genes. However, single strand conformational polymorphism analysis of all 3 exons of the p16 gene and both exons of the p15 gene failed to demonstrate mutation in any of the 25 cases, and homozygous deletions of the p16 and p15 genes, which are present in some human cancers, were not found in any parathyroid tumors. These observations indicate that inactivating mutations or homozygous deletions of the p16 and p15 genes occur uncommonly, if ever, in parathyroid adenomas; however, loss of a different tumor suppressor gene (or genes) on 9p appears to contribute to the pathogenesis of a significant percentage of these tumors.
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PMID:Loss of chromosome arm 9p DNA and analysis of the p16 and p15 cyclin-dependent kinase inhibitor genes in human parathyroid adenomas. 885 19


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