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)

AIE-75 is a protein identified as an autoantigen in patients with autoimmune enteropathy and as a colon cancer-related antigen. It has recently been assigned to be a causative gene for Usher type 1C congenital syndromic hearing loss. The novel protein has three PSD-95/Dlg/ZO-1 (PDZ) protein-protein interaction domains and is therefore implicated to function as a molecular anchor or sorter. We have identified a novel protein that binds to AIE-75 by yeast two-hybrid screening. The protein has a high homology to the tumor suppressor MCC (mutated in colon cancer; or MCC1 hereafter) and was named MCC2. MCC2 protein binds the first PDZ domain of AIE-75 with its C-terminal amino acids -DTFL. Since the MCC1 does not bind to AIE-75 and the MCC2 displays different expression patterns in various organs compared to MCC1, they appear to play distinct roles in cells. The MCC2 gene is located on chromosome 19p13 in the vicinity of APCL gene, while MCC1 maps near to APC tumor suppressor gene. Because of negative expression of MCC2 in a panel of cancer cell-lines compared to the corresponding normal tissues, we suggest that further study is necessary to investigate a possible role of MCC2 as a tumor suppressor.
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PMID:Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ-domain Protein AIE-75. 1131 60

Samples of Barrett metaplastic specialized epithelium (SE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive adenocarcinoma (CA) derived from 36 esophagectomy specimens were studied for loss of heterozygosity (LOH) in APC and MCC and for expression of APC protein. Of 18 cases that were heterozygous (informative) for APC, LOH was found in none of 14 SE samples, 2 of 8 LGD samples, 3 of 11 HGD samples, and 5 of 17 CA samples. Immunohistochemically, markedly reduced expression of APC protein (< 50% positive cells) was found in 3 of 19 HGD samples and 4 of 35 CA samples but not in SE or LGD samples. Of 17 cases informative for the MCC gene, LOH was detectable in 1 of 14 SE samples, none of 7 LGD samples, none of 9 HGD samples, and 4 of 16 CA samples. Allelic loss of APC and/or loss of APC protein expression occurs earlier in the metaplasia-dysplasia-carcinoma sequence in Barrett esophagus than LOH in the MCC gene. The determination of alterations at APC or MCC would be of limited importance for the surveillance of patients with Barrett esophagus.
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PMID:Allelic loss involving the tumor suppressor genes APC and MCC and expression of the APC protein in the development of dysplasia and carcinoma in Barrett esophagus. 1133 78

Twenty-six gastric carcinoma and matching normal tissue DNAs, which had previously been analyzed for alterations of the APC (adenomatous polyposis coli) and MCC (mutated in colorectal cancer) genes were further investigated for the following genetic alterations: mutation and loss of heterozygosity (LOH) of the p53 gene, replication error (RER) and LOH at 12 microsatellite repeat loci, and mutation of the hMSH2 gene. In addition, 9 of the 26 gastric carcinomas were analyzed for genetic alterations using comparative genomic hybridization (CGH). Somatic mutations of the p53 gene were found to be frequent being detected in 31% of gastric carcinomas while LOH at the p53 locus was observed in 37.5% of informative cases. Loss of wild type p53 allele was detected in the majority (7 of 8) tumors found to be harboring a mutation. In the hMSH2 gene, an intronic 4 base pair insertion at 31 base pairs upstream of the beginning of exon 13 was detected in both tumor and normal tissue from one gastric carcinoma case. RER was detected in 11.5% of gastric carcinomas, at one or more microsatellite repeat loci. Of the 12 microsatellite repeat loci analyzed LOH was most frequently observed at D22S351 (30% informative cases) suggesting that a tumor suppressor gene on 22q may be important in gastric carcinogenesis. In support of this, CGH analysis carried out on 9 of the gastric carcinomas identified loss of chromosome 22 in 5 of these tumors.
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PMID:Genetic alterations in gastric cancers from British patients. 1137 3

In 10 cases of Barrett adenocarcinoma, samples from 8 tumor areas (including superficial and deep from peripheral and central areas) and a regional lymph node metastasis were studied for amplification of c-myc, c-erbB-2, and EGFR. We analyzed loss of heterozygosity (LOH) at 3 loci (APC, MCC, and RB) and 2 anonymous microsatellite markers (D4S1652 and D18S474). We detected c-myc in variable fractions of tissue samples from 3 of 9 tumors; EGFR was amplified in 2 specimens from 1 tumor. One tumor demonstrated amplification of c-erbB-2 in all areas. LOH at the D4S1652, MCC, RB, APC, and D18S474 loci was found in 75% (3/4), 57% (4/7), 50% (4/8), 11% (1/9), and 0% (0/10) of informative cases, respectively. LOH generally was restricted to variable subpopulations of tumor cells within individual tumors. There was no obvious association of certain genetic alterations with topographically distinct tumor regions; however, superficial areas showed more frequent genetic alterations than areas from the deeply invading front. More aberrations were detected in the periphery than in the center. Barrett adenocarcinoma is characterized by marked intratumoral genetic heterogeneity, which must be considered when evaluating genetic alterations as indicators of response to therapy and prognosis.
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PMID:Intratumoral genetic heterogeneity in Barrett adenocarcinoma. 1193 30

Small-cell neuroendocrine carcinoma (SCNC) is a well characterized malignancy with distinctive cellular morphology and aggressive biologic behavior most frequently encountered in the lung but also noted for origin from other sites. The basis for this difference in incidence and the impact of primary site location on the molecular pathogenesis of the neoplasm is not well understood. To address this issue and to identify reliable molecular markers of potential diagnostic value for primary site localization of this tumor, we have compared the genetic profile of cancer-related gene damage of SCNC arising from a variety of organ sites. The analysis involved microdissected paraffin-embedded formalin fixed specimens of SCNC. Tumors were organized into 3 groups: lung (n = 18), head and neck region (n = 5), and gastrointestinal tract (n = 5). Genotyping evaluated allelic imbalance (loss of heterozygosity) involving genomic regions containing p53 (17p13), L-myc (1p34), OGG1 (3p26), MCC/APC (5q21), p16 (9p21), PTEN (10q23), and point mutational change in K-ras-2 (12p12) using polymerase chain reaction-based microsatellite analysis and DNA sequencing. Distinct genotypic profiles of allelic imbalance using this panel was seen for each group of SCNC enabling primary site determination to be suggested based on genotypic profiling of microdissected tissue samples. Despite similarity in histologic appearance, our study suggests that SCNC have a unique pattern of acquired allelic damage that is determined in part by primary site of tumor development. These attributes can be effectively used for primary localization of metastatic SCNC, thereby assisting in the diagnosis and classification of this neoplasm.
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PMID:Small-cell neuroendocrine carcinoma displays unique profiles of tumor-suppressor gene loss in relationship to the primary site of formation. 1237 19

Stage I non-small cell carcinoma (NSCLC) of the lung is typically treated with surgery alone, but with a 30 to 40% recurrence rate. Prognostic factors to stratify these patients into high- and low-risk groups would be of significant clinical value, but published data are conflicting. We studied 39 Stage I NSCLC treated with resection alone, followed for a minimum of 5 years, and divided into recurrent (RC) and non-recurrent (NRC) groups (n = 12 and 27, respectively). Allelic imbalance (loss of heterozygosity, LOH) involving genomic regions containing L-myc (1p32), hOGG1 (3p26), APC/MCC (5q21), c-fms (5q33.3), p53 (17p13), and DCC (18q21), and point mutational change in K-ras-2 (12p12) were studied by PCR-based microsatellite analysis and DNA sequencing. Mutations in k-ras-2 were seen in 25% and 19% of RC and NRC tumors, respectively, most frequently in adenocarcinomas. LOH in the RC and NRC respectively were 50% and 37% for L-myc, 60% and 33% for hOGG1, 60% and 50% for APC, 38% and 35% for c-fms, 78% and 75% for p53, and 17% and 45% for DCC. No statistical significance was seen comparing any of the allelic alterations with recurrence. LOH for hOGG1 and L-myc were more commonly seen in squamous cell carcinomas. Stage I NSCLC are genetically heterogeneous with respect to mutation acquisition. The approach of investigating a panel of genes for alterations can be applied to any given tumor type, and provides information on patterns of mutations/LOH that can help us better understand the molecular biology of tumorigenesis.
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PMID:Widespread molecular alterations present in stage I non-small cell lung carcinoma fail to predict tumor recurrence. 1252 10

In order to assess the role of the changes of DCC and APC/MCC genes in the development and progression of gastric cancer, the loss of heterozygosity (LOH) of these genetic loci was investigated in 45 surgical specimens of gastric cancer with PCR-RFLP. The rate of LOH was 30.0% (9/30) at APC/MCC gene and 33.3% (15/45) at DCC gene. LOH was found in both intestinal and gastric types of gastric cancer and the rate of LOH of DCC gene was significantly higher in stages III to approximately IV gastric cancer (48.0%) than in stages I to approximately II (15.0%) (P<0.05). LOH of APC/MCC gene could be found in both early and advanced stages of gastric cancer. These findings suggest that changes of DCC and APC/MCC genes are involved in the development and progression of the intestinal and gastric types of gastric cancer.
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PMID:Study of loss of heterozygosity at DCC and APC/MCC genetic loci of gastric cancer. 1290 20

The incidence/mortality rates of esophageal squamous cell carcinoma (ESCC) vary widely in different parts of China. Human papillomavirus (HPV) infection is considered a possible risk factor. Loss of heterozygosity (LOH) analysis on 87 ESCC specimens collected from three different areas of China showed lower frequency of LOH at marker D3S1621 in Linxian, an area with exceptionally high incidence of ESCC but low HPV infection rate. HPV-positive ESCC from Hong Kong, but not Sichuan, had higher frequency of LOH at D5S82 (APC, MCC), D6S497 (p21/Waf-1, HLA) and D13S260 (BRCA2) than HPV-negative samples. Our results suggest that different genetic pathways of carcinogenesis may be associated with geographic differences in risk factors.
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PMID:Human papillomavirus infection and loss of heterozygosity in esophageal squamous cell carcinoma. 1532 39

Colorectal carcinomas are characterized by multiple genetic aberrations that occur during tumorigenesis. Several tumor suppressor genes associated with colorectal carcinoma have been identified: MCC, APC, p53, nm23-H1, DCC, DPC4. We examined 73 cases of sporadic human colon cancer and corresponding normal tissue samples to evaluate the loss of heterozygosity (LOH) at the APC gene loci. The purpose of this study was also to evaluate whether the LOH at the APC gene is associated with clinicopathological characteristics in sporadic colon cancer. We also investigated presence and the frequency of the most common APC gene mutations and APC E1317Q and I1307K germ-line variants in Croatian colorectal cancer patients. Five markers in all patients were found to be heterozygous and informative for LOH analysis. LOH at the APC locus was detected in 30.1% of tumors were examined. The majority of APC gene LOH was observed in Dukes' B (55.6%) and in the moderately differentiated tumors (42.9%). Only 1309 APC gene mutation was detected in our samples. In one tumor sample, a new sporadic mutation of the APC gene in codon 1374 was detected. APC E1317Q and I1307K germ-line variants were not detected in our population. But APC E1317Q sporadic mutation was found in one tumor sample.
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PMID:APC gene loss of heterozygosity, mutations, E1317Q, and I1307K germ-line variants in sporadic colon cancer in Croatia. 1550 35

Germline mutations of the APC gene are responsible for familial adenomatous polyposis (FAP). Most of the mutations are protein truncating mutations and are spread over the coding region. Rare whole-gene deletions or exonic deletions have been described. From a series of 85 patients clinically diagnosed with FAP or attenuated FAP (AAPC) in our center, 30 (35%) were found to have truncating or missense mutations. We have now screened the remaining 55 patients for exonic deletions or duplications, first by semi-quantitative PCR and later by multiplex ligation-dependent probe amplification (MLPA). Three whole-gene deletions and one exon 14 deletion were found (5% of patients). The whole-gene deletions were confirmed by fluorescence in situ hybridization (FISH) analysis, and the breakpoints of the exon 14 deletion could be determined using long range PCR. Further characterization of the whole gene deletions was performed using extragenic polymorphic markers and/or semi-quantitative PCR. We could demonstrate that the deletions do not encompass the MCC gene. Interestingly, the phenotype of the deletion patients was not different from that of patients with truncating mutations. The polyp numbers ranged from attenuated to profuse polyposis and the interfamilial variability of disease phenotype was as in other FAP families. In none of the 28 AAPC patients included in this study, was a large deletion found, while 15% of the patients with classical polyposis had a genomic deletion. It corroborates recently published data, suggesting that large deletions may occur with a frequency higher than 10% in mutation-negative patients with a classical polyposis. In this article, we have included an overview of genomic rearrangements in the 5q21 region.
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PMID:Large deletions of the APC gene in 15% of mutation-negative patients with classical polyposis (FAP): a Belgian study. 1564 2


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