Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Papillary thyroid carcinoma (PTC) is one of several tumours associated with familial adenomatous polyposis (FAP), an inherited tumour syndrome which appears to result from germ-line mutation of the APC tumour suppressor gene. Here we investigate the possibility that somatic mutation of APC might play a role in sporadic PTC. 16 cases of PTC together with matched normal tissue were examined by single-strand conformation polymorphism (SSCP) analysis, concentrating on the mutation cluster region (MCR) of the APC gene (codons 1286-1513). No evidence of mutation was observed in any sample. We conclude that APC mutation, at least in the MCR, is not a significant causal mechanism in sporadic PTC.
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PMID:Evidence against involvement of APC mutation in papillary thyroid carcinoma. 794 97

Germ-line mutations of the adenomatous polyposis (APC) gene, responsible for familial adenomatous polyposis (FAP) were analyzed in 15 patients with FAP-associated papillary thyroid carcinomas: 13 had the mutation between codons 778 and 1309 (exon 15), 1 at codon 593 (exon 14), and 1 at codon 140 (exon 3). Therefore APC gene mutations clustered in the genomic area associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE) (codons 463-1387). Ocular patches were documented in 12 patients. In particular, 4 of the 15 patients, all women with a mean age of 23.5 (range 20-32), were found during the study of 15 consecutive kindreds who had undergone systematic screening for extra-colonic manifestations. Three of them belonged to the same kindred and were asymptomatic. These four patients were also screened for loss of heterozygosity of APC in the thyroid tumoral tissue. No biallelic inactivation of the APC gene was found. In contrast, three of these four patients had activation of the ret-PTC oncogene. In particular, there was activation of the ret-PTC1 isoform, a chimeric gene resulting from fusion of a gene named H4 with the RET gene. On histologic examination, three of the four patients showed Hashimoto-like lymphocytic infiltration. Present data suggest that: (1) the incidence of FAP-associated thyroid cancer probably has been underestimated in the past; (2) intensive screening could detect a larger than expected number of thyroid carcinomas; (3) systematic screening is recommended in patients with ocular patches and genetic mutation in exon 15; (4) Hashimoto-like findings do not exclude carcinoma but are a frequent accompanying finding; (5) despite frequent multicentricity and early lymph node involvement, FAP-associated thyroid tumors seem to have an excellent prognosis, in particular those showing ret-PTC activation.
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PMID:Genetic alterations in thyroid carcinoma associated with familial adenomatous polyposis: clinical implications and suggestions for early detection. 984 49

We report two familial adenomatous polyposis (FAP) kindreds with thyroid cancer, harboring two apparently novel germlineAPC mutations. The clinical phenotype in the first kindred was typical of classical adenomatous polyposis, whereas the second kindred exhibited an attenuated adenomatous polyposis phenotype. There was a female predominance with a mean age of 34 years (range, 23-49) at cancer diagnosis. Multiple sections of four thyroid tumors from three FAP patients were analyzed in detail. Histological examination of thyroid tumors showed a range of morphological features. Some tumors exhibited typical papillary architecture and were associated with multifocal carcinoma; in others, there were unusual areas of cribriform morphology, and spindle-cell components with whorled architecture. Immunoreactivity for thyroglobulin and high molecular weight keratins was strong. Somatic APC mutation analysis revealed an insertion of a novel long interspersed nuclear element-1-like sequence in one tumor sample, suggesting disruption of APC. In three FAP patients, ret/PTC-1 and ret/PTC-3 were expressed in thyroid cancers. No positivity was observed for ret/ PTC-2. p53 immunohistochemistry was positive in only one section of a recurrent thyroid tumor sample. Our data suggest that genetic alterations in FAP-associated thyroid cancer involve loss of function of APC along with the gain of function of ret/PTC, while alterations of p53 do not appear to be an early event in thyroid tumorigenesis.
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PMID:Familial adenomatous polyposis-associated thyroid cancer: a clinical, pathological, and molecular genetics study. 991 27

Recent studies have mapped two susceptibility loci which appear to account for familial multinodular goitre (MNG1) and a variant of familial papillary thyroid cancer (PTC), with associated multinodular goitre (TCO). A Tasmanian family (Tas1) has been identified with an autosomal dominant form of PTC. This study has examined the MNG1 and TCO loci to determine if they are similarly predisposing the Tas1 family to PTC. Linkage analysis using identical microsatellite markers described in the two previous studies was used to determine the significance of these loci in the Tasmanian family. The resultant LOD scores were sufficiently negative using multipoint parametric analysis to exclude these two loci from involvement in the Tasmanian family. In addition, six candidate genes, RET, TRK, MET, TSHR, APC and PTEN were also excluded as susceptibility genes in Tas1 by using microsatellites that are positioned in or in close proximity to these genes. These results suggest that there are at least three susceptibility genes that predispose families to familial PTC.
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PMID:At least three genes account for familial papillary thyroid carcinoma: TCO and MNG1 excluded as susceptibility loci from a large Tasmanian family. 1042 54

Papillary thyroid carcinoma (PTC) is one extracolonic manifestation affecting about 1-2% of patients with familial adenomatous polyposis (FAP). Ninety-seven patients with FAP-associated PTC have previously been reported, including 6 pairs of siblings. During a European collaborative study, 15 patients with FAP-associated PTC were collected. All 15 patients were females. The mean age at thyroidectomy was 24.9 yr (range, 19-39 yr). In 13 subjects, APC germline mutations had been detected; they were at codons 140, 593, 778, 976, 993, 1061 (n = 5), 1105 (n = 1), and 1309 (n = 2), respectively. A review of the literature added 11 other patients with FAP-associated PTC and detection of germline APC mutations; they were at codons 313 (n = 2), 698 (n = 3), 848 (n = 2), 1209 (n = 2), 1061 (n = 1), and 1105 (n = 1), respectively. The latter led to formation of the same stop codon (TAA) at 1125-1126 as the mutation at codon 1061. Therefore, 21 of 24 mutations were in exon 15 in the genomic area usually associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE), i.e. codons 463-1387. Typical CHRPE was found in 17 of 18 affected patients who had specific screening. Interestingly, 22 of the 24 patients had their mutation out of the mutation cluster region (codons 1286-1513), which is currently considered the hot spot mutation area, in particular for extracolonic manifestations of FAP. The difference in the incidence of germline mutations before and after codon 1220 between PTC and non-PTC FAP patients was statistically significant (P<0.05) for both patients and kindreds (P = 0.005 and P = 0.049, respectively). Even if most mutations were scattered throughout the entire 5'-portion of exon 15, 8 of 23 patients (6 with mutation at 1061 and 2 with mutation at 1105; i.e. more than one third) had the same truncated protein product. The awareness that patients with PTC usually have APC mutations that cluster in a well defined genomic area, in addition to giving a deeper insight into gene function, could facilitate both earlier diagnosis and better treatment. In particular, intensive screening for thyroid nodules after age 15 yr is recommended when a single patient or an entire kindred have CHRPE and/or mutations in the 5'-portion of exon 15.
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PMID:Germline mutations of the APC gene in patients with familial adenomatous polyposis-associated thyroid carcinoma: results from a European cooperative study. 1123 50

Chronic hemodialysis (HD) may lead to losses of carnitine from plasma and muscle. Plasma carnitine does not reflect the body content of carnitine. The purpose of this study was the evaluation of total and free plasma and muscle carnitine concentrations (TPC, FPC, TMC, FMC), muscle glycogen and the relationship between plasma and tissue carnitine content and the basic indices of lipid metabolism in HD patients. The studies were conducted in two groups: the first one consisted of 37 HD patients (19 F, 18 M), the second one served as the control and was composed of 29 (10 F, 19 M) patients with healthy kidneys. Tissue specimens in HD patients were taken during surgery on arterio-venous fistula from brachioradial muscle. Carnitine and glycogen measurements were performed using enzymatic methods according to Cederblad and Huijng respectively. Total cholesterol (CH), HDL-CH, and triglycerides were assayed by enzymatic commercial test system (Boehringer-Mannheim, Germany). To summarise, we found the following phenomena in our HD patients in comparison with the controls: 1) In plasma: similar TPC but decreased FPC levels and FPC/TPC ratio which may suggest free carnitine deficiency. 2) In muscle: significantly lower TMC and FMC levels but normal FMC/ITMC ratio. 3) Negative correlation between TMC and FMC levels and duration of dialysis treatment. 4) No correlation between plasma and muscle camitine concentration. 5) Significantly higher concentration of muscle glycogen which could be explained by the changes in the structure of muscle fibres in HD patients and/or lower physical activity. 6) A positive correlation between FPC/APC or FPC/TPC ratio and HDL-CH in HD patients which may suggest that an appropriate proportion between free and acylcarnitines may influence HDL-CH levels in that population.
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PMID:Correlation between plasma carnitine, muscle carnitine and glycogen levels in maintenance hemodialysis patients. 1074 3

The Authors report 9 patients who were affected by familial papillary carcinoma of thyroid These patients were members of 4 families and they were selected in a general group of 97 patients affected by papillary cancer of the thyroid who underwent surgery from 1991 to 1998. The 9 patients were 1st degree relatives: two sisters, two sisters, two sisters and three brothers. The clinical course was similar in patients whether familiar or sporadic group, but average age in first was 10 yrs lower than in the latter group. Functional cervical dissection was needed only one time by lymphatic metastasis. Observed survival was 100% (follow up 92-16 months) and no specific complication was reported. Thyreoglobulin value was less than normal in every patients. Ret linkage analysis was always performed and no rearrangement was found; in 4 patients APC gene was detected but it was never seen. Case studies are consistent with an autosomal dominant trait that shows an high penetrance if associated with a permissive codominant trait. The authors believe that are necessary further studies on this occurrence. In papillary thyroid cancer familiarity was observed in 9.6%, than authors propose that relatives of thyroid papillary cancer should be underwent to screening.
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PMID:[Familial papillary carcinoma of the thyroid: biogenetic identification and clinical assessment of 4 families]. 1176 42

Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, and murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.
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PMID:Medulloblastoma: molecular genetics and animal models. 1525 53

We report a case of a 23-year-old Turcot female patient who was first diagnosed as having a pinealoblastoma. Thyroid papillary carcinoma was diagnosed a few months later, and multiple colonic polyps were detected three years after that. A genetic workup revealed an APC gene mutation in her family. Long-term survival (i.e., >5 years) of pinealoblastoma is considered to be 20 percent. A review of 25 documented Turcot cases determined that the average age at death is 20.3 years, raising the difficult question of whether she should undergo restorative proctocolectomy. Restorative proctocolectomy may itself cause major morbidity but is currently the only way to prevent colon cancer.
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PMID:Pinealoblastoma in a patient with familial adenomatous polyposis: variant of Turcot syndrome type 2? Report of a case and review of the literature. 1640 May 11

We describe an uncommon thyroid tumor in a 56-year-old woman. The widely infiltrating, angioinvasive neoplasm, 5 cm in diameter, exhibited a peculiar architectural growth pattern characterized by follicles with round to oval epithelial tufts growing within, often supported by a fibrovascular core mimicking the renal glomerulus. Colloid-empty follicles, tubular or elongated, were lined by pseudostratified tall, columnar cells with clear cytoplasm. Nuclei were round to oval, with evenly distributed, slightly coarse chromatin. Tumor cells were positive for thyroid transcription factor-1, thyroperoxidase, thyroglobulin, cytokeratin 18, Hector Battifora mesothelial cell, and vimentin. Scattered cells positive for S100, Wilms tumor 1 (WT1), and cytokeratins AE1/AE3 were found, with no reaction detected for cytokeratins 34betaE12, 5/6, 7, 19, or 20. There were PAX8-PPARgamma rearrangement and N-RAS mutation. No mutations were found for APC or BRAF genes, nor were RET/PTC rearrangements detected. Because of the distinctive histologic features, we propose naming this tumor follicular thyroid carcinoma with an unusual glomeruloid pattern of growth.
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PMID:Follicular thyroid carcinoma with an unusual glomeruloid pattern of growth. 1860 67


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