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)

Until now only Japanese authors have reported 4 cases of pancreatic neoplasm associated with ulcerative colitis (UC). We report on a case of a 44-year-old woman who was operated on for complicated UC and an exocrine-endocrine neoplasm of the pancreas, where the endocrine component was presented by pancreatic polypeptide (PP)-producing cells. By means of molecular genetics methods we found microsatellite instability (MSI) in the markers D18S35, FGA and p53 in the colonic lining, and loss of heterozygosity (LOH) in the p53 marker in the pancreatic tumor. A literature review concerning the coexistence of these two conditions showed that PP is involved in the pathogenesis of the UC and that UC increases the risk of development of extracolonic neoplasms.
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PMID:A case of exocrine-endocrine neoplasm of the pancreas in a patient with ulcerative colitis with literature review. 1741 36

Thyroid carcinoma is the most common endocrine neoplasm and the seventh most frequent human malignancy. It can be distinguished into differentiated and undifferentiated. Differentiated tumors include those arising from thyrocytes, i.e. papillary and follicular carcinoma, while medullary carcinoma originates from parafollicular or C cells. Anaplastic carcinoma comprises undifferentiated tumors. The factors inducing thyroid carcinoma development are not fully understood despite some well-established associations, such as the one between ionizing radiation and papillary carcinoma and that between iodine deficiency and follicular carcinoma. Genetic investigations of differentiated thyroid tumors have documented mutation of genes involved in the regulation of MAP kinase pathway activation in papillary carcinoma, and of genes involved in the regulation of the PI3 kinase pathway in follicular carcinoma. Analysis of their clinical course and of positivity for mutations has demonstrated that prognosis is greatly affected by the type of mutated gene. Genetic investigations therefore have the potential to direct diagnosis, but especially to tailor therapy and follow-up to the individual patient and even the individual gene. Anaplastic carcinoma, a highly aggressive, undifferentiated form, can arise as such or else be the de-differentiated progression of a papillary or a follicular carcinoma. It displays a mutated tumor suppressor gene (p53), which is crucial in the regulation of cell apoptosis, in addition to the mutations found in papillary and follicular forms. Medullary carcinoma is a malignant neoplasm with an intermediate clinical course between differentiated and undifferentiated forms. It manifests more frequently as a sporadic neoplasm or as a familial MEN. The latter is a high-penetrance, autosomal dominant hereditary disorder. Identification of the gene responsible for medullary carcinoma has radically changed the diagnostic approach to the familial forms, enabling early neonatal diagnosis of mutation carriers and of the disease, and early surgical approach by prophylactic thyroidectomy. Genetic studies have significantly affected the endocrinologist's diagnostic approach, as in the case of medullary carcinoma; over the next few years they are expected to provide further information to tackle papillary and follicular thyroid carcinoma. This review addresses the main genetic mutations responsible for neoplastic transformation in thyroid disorders.
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PMID:Genetic mutations in thyroid carcinoma. 1920 25

Two juxtaglomerular cell tumors (JGCTs) were investigated in comparison with 14 endocrine tumors of the pancreas (ETPs), focusing on the cell cycle, apoptosis, and cytogenetic changes. JGCTs revealed nuclear accumulation of Cyclin D(1), together with the cyclin-dependent kinase inhibitors p21(Cip1/Waf1) and p27(Kip1). In contrast, no accumulation of Cyclin D(3), p53, p16(INK4a), or Mdm-2 was seen. Bcl-2 protein was intensively, but Rb only moderately, expressed. This immunoreactive profile was not found in the ETPs, which were negative for Bcl-2, p27(Kip1), p21(Cip1/Waf1), and - with one exception - for Cyclin D(1) (1/14) but expressed Cyclin D(3) in 7/14 cases. JGCTs displayed characteristic genetic alterations with combined losses of chromosomes 9, 11, 15, and 21 and gains of chromosome 18. In contrast, no characteristic pattern of genetic alterations was found in ETPs. In both, the amount of chromosomal aberrations correlated with tumor size. In small ETPs and JGCTs, genetic losses dominated over gains of chromosomes, whereas in large/malignant ETPs, gains and losses were equally affected. Thus, JGCTs represent a special type of renal endocrine neoplasm characterized by deregulation of cell cycle components and a typical profile of chromosomal aberrations. Since only two JCTs were investigated, further studies for validation of these results are, however, necessary.
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PMID:Dysregulation of the cell cycle and chromosomal imbalances in juxtaglomerular cell tumors - a comparative study with endocrine tumors of the pancreas. 2148 36

Thyroid papillary carcinoma is the most common endocrine neoplasm and generally carries a favorable prognosis. However, a small subset of papillary carcinomas transforms into anaplastic carcinoma, an undifferentiated cancer with a dismal prognosis. Recent studies using next-generation sequencing revealed the genomic landscape of papillary carcinoma and anaplastic carcinoma. However, risk factors for anaplastic transformation in papillary carcinoma remain obscure. In the present study, we investigated molecular alterations of papillary carcinoma and anaplastic carcinoma components in 27 tumors in which anaplastic carcinoma coexisted with antecedent papillary carcinoma. We conducted direct sequencing for BRAF, TERT promoter and PIK3CA, and immunohistochemistry for p53, TTF-1 and subunits of the SWI/SNF complex (ARID1A, ARID1B, ATRX, SMARCA2, SMARCA4, SMARCB1, and PBRM1). BRAFV600E and TERT promoter mutated at the rate of 90% and 95%, respectively, and these mutational statuses were almost identical between the papillary carcinoma and anaplastic carcinoma components. PIK3CA mutation was positive in 33% of our samples with a heterogeneous mutation pattern of the papillary carcinoma and anaplastic carcinoma components. Aberrant expression of p53 and loss of TTF-1 were present in 63 and 59%, respectively, and these two alterations were confined to the anaplastic carcinoma components. There was a loss of the SWI/SNF complex in a subset of the tumors with a heterogeneous pattern of the papillary carcinoma and anaplastic carcinoma components: SMARCA4 in 4% and PBRM1 in 4%. In a multivariate comparison between the antecedent papillary carcinoma components and control papillary carcinomas without anaplastic transformation, TERT promoter mutation was independently associated with anaplastic transformation. Collectively, papillary carcinoma-derived anaplastic carcinomas are characterized by BRAF and TERT promoter mutations, and these mutations occur prior to anaplastic transformation. Alterations of PIK3CA and the SWI/SNF complex are relatively rare and temporally heterogeneous. Of note, a papillary carcinoma harboring TERT promoter mutation is at higher risk for anaplastic transformation.
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PMID:Molecular alterations of coexisting thyroid papillary carcinoma and anaplastic carcinoma: identification of TERT mutation as an independent risk factor for transformation. 2873 Oct 42