Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focal nodular hyperplasia (FNH) is considered a benign tumor of the liver. However, the biologic nature and clonality status of FNH are not well established. We sought to determine the clonality and TP53 mutation status of FNH to better characterize the nature of FNH. We analyzed 15 cases of FNH from female patients who underwent surgical resection of their lesions. Genomic DNA was extracted from paraffin-embedded tissue sections using laser-capture microdissection and analyzed for X-chromosome inactivation status and TP53 mutations by direct DNA sequencing. Thirteen cases were informative for X-chromosome inactivation analysis. Of the 13 informative cases, 4 (31%) showed a nonrandom pattern of X-chromosome inactivation, consistent with monoclonal origin. No TP53 mutations were detected in any of the FNH cases. The clonality status was not associated with any clinicopathologic parameters such as age and lesion size. Our data indicate that a significant proportion of FNH lesions have a monoclonal origin, suggesting that they are neoplastic rather than reactive.
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PMID:Clonality and TP53 mutation analysis of focal nodular hyperplasia of the liver. 2055 Dec 68

Cervical neuroendocrine carcinomas are rare, aggressive tumors and their immunohistochemical features and clonal relationship to coexisting tumors are incompletely described. Twenty-eight cases were identified (17 small cell, 9 large cell, and 2 mixed), 10 of which had an invasive squamous or adenocarcinoma component. Staining for synaptophysin, chromogranin A, TTF1, c-kit, CD44, and p16 was performed. Analyses for loss of heterozygosity (LOH) at 5 polymorphic microsatellite markers (D3S1300, D9S171, D11S914, D13S319, and TP53) and X-chromosome inactivation were performed. Of 17 cases with available blocks, 13 (76%) were synaptophysin+, 8 (47%) were chromogranin A+, 8 (47%) were TTF1+, 7 (41%) were c-kit+, and 6 (35%) were CD44+. Strong patchy or strong diffuse p16 staining was seen in all cases. LOH and X-chromosome inactivation analysis were performed for 17 cases, 8 of which had a coexisting squamous or adenocarcinoma component. Five of the 8 (63%) cases with 2 components showed allelic loss in both components. All 5 of these cases demonstrated identical LOH between the neuroendocrine and squamous or adenocarcinoma components. Nonrandom X-chromosome inactivation was seen in the neuroendocrine and other components in 4 of the 8 cases. In all 4 cases the pattern of inactivation was identical between the 2 components. Cervical neuroendocrine carcinomas have features similar to other extrapulmonary neuroendocrine carcinomas, including expression of TTF1, c-kit, and CD44. Consistent staining for p16 is also seen. Concordant genetic alterations support common clonal origin for neuroendocrine carcinomas with a coexisting squamous or adenocarcinoma component.
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PMID:Cervical Carcinomas With Neuroendocrine Differentiation: A Report of 28 Cases With Immunohistochemical Analysis and Molecular Genetic Evidence of Common Clonal Origin With Coexisting Squamous and Adenocarcinomas. 2663 Feb 33

In our previous work, we established an in vitro variant of the currently developed in vivo PIG-A assay as promising mutagenicity test system. We applied the human B-lymphoblastoid cell line TK6 for the in vitro assay development, which is based on the cellular glycosylphosphatidylinositol (GPI) status. At least 22 genes are involved in GPI biosynthesis, leading to the complex situation that, in principle, multiple genes could induce a GPI-deficient phenotype by acquiring inactivating mutations. However, only the PIG-A gene is located on the X-chromosome, rendering PIG-A more sensitive compared to autosomal linked, GPI-relevant genes. In this work, we investigated the GPI-related genotype-to-phenotype relationship in TK6 cells. By a next-generation sequencing approach, we identified a heterozygous chromosomal deletion on chromosome 17, where the PIG-L gene is located. In the analyzed TK6 cell clones, the GPI-deficient phenotype was induced either by mutations in PIG-A, by the complete absence of PIG-A mRNA, or by deletions in the remaining functional PIG-L gene, causing loss of heterozygosity. The identified PIG-L heterozygosity could also be responsible for the increased sensitivity toward mutagenic ethyl methanesulfonate or UV-C treatments of p53-proficient TK6 compared to the TK6-related, but p53-deficient WI-L2-NS cell line. Moreover, the WI-L2-NS cell line was found to exhibit a much lower number of GPI-deficient mutant cells in the purchased cell batch, and WI-L2-NS exerted a lower spontaneous rate of GPI deficiency compared to TK6 cells.
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PMID:The in vitro PIG-A gene mutation assay: glycosylphosphatidylinositol (GPI)-related genotype-to-phenotype relationship in TK6 cells. 2710 Jan 16

Individuals with robust natural killer (NK) cell function incur lower rates of malignancies. To expand our understanding of genetic factors contributing to this phenomenon, we analyzed NK cells from cancer resistant and susceptible strains of mice. We identified a correlation between NK levels of the X-chromosome-located adaptor protein SLy1 and immunologic susceptibility to cancer. Unlike the case for T or B lymphocytes, where SLy1 shuttles between the cytoplasm and nucleus to facilitate signal transduction, in NK cells SLy1 functions as a ribosomal protein and is located solely in the cytoplasm. In its absence, ribosomal instability results in p53-mediated NK cell senescence and decreased clearance of malignancies. NK defects are reversible under inflammatory conditions and viral clearance is not impacted by SLy1 deficiency. Our work defines a previously unappreciated X-linked ribosomopathy that results in a specific and subtle NK cell dysfunction leading to immunologic susceptibility to cancer.
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PMID:Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance. 2812 74


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