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)

We examined the genomic status of the CDKN2 gene including de novo methylation of 5' CpG islands in primary and metastatic tumor samples from 31 patients with esophageal squamous cell carcinoma. One somatic frame shift mutation (1 of 31; 3.2%) was identified by PCR-single strand conformational polymorphism analysis and DNA sequencing. Homozygous deletion and de novo methylation of the gene were confirmed in 5 (16%) and 6 (19%) of 31 patients, respectively. Homozygous deletion and de novo methylation were significantly associated with silencing of gene expression (P < 0.01). Aberrations of the CDKN2 gene were detected in tumors with lymph node metastasis and muscular invasion (12 of 22; 54%) and in none of stage I tumors (0 of 9.0%; P < 0.05). These results suggest that homozygous deletion and de novo methylation are predominant mechanisms of inactivation of the CDKN2 gene and may be associated with metastatic and invasive phenotypes of esophageal squamous cell carcinoma.
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PMID:Inactivation of the CDKN2 gene by homozygous deletion and de novo methylation is associated with advanced stage esophageal squamous cell carcinoma. 875 49

Inactivation of the cyclin-dependent kinase inhibitor p16INK4a (CDKN2/MTS1) is documented in a wide variety of cancer cell lines and tumors. We have shown that loss of p16INK4a protein expression is a common event in early stage non-small cell lung cancer (NSCLC), correlates with a significantly worse survival, and is more common in higher stage disease. One hundred NSCLC tumors from patients undergoing definitive thoracotomies at a single institution were examined for p16INK4a and retinoblastoma protein (pRB) expression. Abnormal pRB staining was identified in 15% of the tumors, whereas 51% possessed aberrant p16INK4a protein expression. Tumors with aberrant expression of p16INK4a by immunohistochemistry were associated with a significantly worse survival (P=0.04). Additionally, the inverse correlation of pRB and p16INK4a expression previously noted in lung cancer cell lines and tumors was confirmed in this large cohort of patients, with 65% of the tumors demonstrating inverse expression of pRB and p16INK4a (p=0.00019). A statistically significant increase in aberrant p16INK4a expression, as well as inverse expression of p16INK4a and pRB, was seen with increasing pathological stage of disease. These findings establish the prognostic significance (of the absence of p16INK4, in resected NSCLC and confirm the critical importance of disrupting the pathway of cyclin-dependent kinase-mediated phosphorylation of pRB in the molecular oncogenesis and progression of NSCLC.
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PMID:Rb and p16INK4a expression in resected non-small cell lung tumors. 875 4

We analyzed the p16INK4 status of 6 hepatocellular carcinoma (HCC) cell lines and 32 primary HCC tumors, including 9 early-stage tumors, to determine whether p16INK4 tumor-suppressor gene inactivation participates in hepatocarcinogenesis. p16INK4 was studied at its protein level through Western blotting, at its messenger RNA (mRNA) level through reverse-transcriptase polymerase chain reaction analysis (RT-PCR) and Northern blotting, and at its genomic level through Southern blotting and PCR-single-strand conformation polymorphism analysis. The p16 protein was absent from 3 of 6 cell lines (50%) and 11 of 32 primary tumors (34%), but present in noncancerous tissues, indicating that p16INK4 is involved in hepatocarcinogenesis. Furthermore, we suggest that the p16 protein loss may contribute to the following: (1) early-stage hepatocarcinogenesis, because it was observed in 22% of early stage tumors; and (2) tumor progression, because it occurred approximately twice as often in advanced rather than in early stage tumors (40%). It was striking that neither p16INK4 homozygous deletion and mutation nor loss of p16INK4 mRNA expression were observed in HCC cell lines and primary tumors, including those specimens from which the p16 protein was absent except the Li7HM cell line, in which p16INK4 mRNA was not detected. These results suggest that p16INK4 in HCC is inactivated predominantly by posttranscriptional regulation rather than by genomic aberrations and lack of transcription.
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PMID:Inactivation of p16INK4 in hepatocellular carcinoma. 878 27

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

To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene-containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients. Overall, eight angiomyolipomas, eight giant cell astrocytomas, one cortical tuber, and three rhabdomyomas were analyzed. Loss of heterozygosity at either TSC locus was found in a large fraction of the informative patients, both sporadic (7/14) and familial (1/4). Interestingly, a statistically significant preponderance of loss of heterozygosity at TSC2 was observed in the sporadic group (P < 0.01). Among the possible explanations considered, the bias in the selection for TSC patients with the most severe organ impairment seems particularly appealing. According to this view, a TSC2 defect might confer a greater risk for early kidney failure or, possibly, a more rapid growth of a giant cell astrocytoma. None of the seven antioncogenes tested showed loss of heterozygosity, indicating that the loss of either TSC gene product may be sufficient to promote hamartomatous cell growth. Finally, the observation of loss of heterozygosity at different markers in an astrocytoma and in an angiomyolipoma from the same patient might suggest the multifocal origin of the second-hit mutation.
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PMID:Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas. 882 21

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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