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

An unusual case of advanced synchronous colon and gastric carcinoma is described. A 36 year old female was admitted to our Department with a stenosing right colon cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain and gross blood in the stool. Multiple colon polyps, distal to the tumor, were also detected. On preoperative abdominal computed tomography, a stenosing right colon cancer, without evidence of abdominal diffusion, was confirmed. At laparotomy, in addition to colon cancer, an antral gastric cancer was incidentally found. En bloc hemigastrectomy and subtotal colectomy were performed. Digestive continuity was restored by gastrojejunal and ileosigmoid anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2 oncoproteins. No genetic defect was identified in the APC and MMR genes. The patient is alive, without recurrence, two years after the operation.
 ...
PMID:Synchronous colon and gastric advanced carcinomas. 1594 46

Barrett's esophagus is a premalignant condition and remains the number one risk factor for developing adenocarcinoma. Gastro-esophageal reflux disease is a strong risk factor for both esophageal adenocarcinoma and the precancerous lesion Barrett's esophagus. Both of these conditions are related to the reflux of acid and bile into the esophagus. This results in inflammation and cell damage which initiates a sequence of events termed the metaplasia-dysplasia sequence in which the squamous epithelium is replaced by columnar epithelium exhibiting increasing degrees of dysplasia and overt malignancy. The underlying disease mechanisms remain unclear, but tumor suppression genes (p53, p16, APC) and, oncogenes (K-ras, cyclin D1, c-erb-2) seem to cause the malignant transformation of Barrett's esophagus, and the genetic or epigenetic alterations of these genes have been reported.
 ...
PMID:[Carcinogenesis of Barrett's esophagus]. 1610 Dec 21

The development and progression of Barrett's epithelium are accompanied with the acquisition of many molecular changes of the oesophageal mucosa. Gastro-oesophageal reflux and inflammation cause the oxidative stress and free-radical generations, which result in the expression of oxidative-stress-related genes and the induction of DNA damage. The development of Barrett's epithelium follows a metaplasia-dysplasia-adenocarcinoma sequence, characterized by the accumulation of many genetic and epigenetic alterations, which are seen in carcinogenesis. Abnormalities in the expression of tumor suppressor genes, such as p53, p16, APC, and a number of molecules involved in cell proliferation, apoptosis or angiogenesis are observed. These genetic alterations affecting the cancer hallmarks provide a better understanding of the etiology and pathogenesis of the disease.
 ...
PMID:[Molecular events associated with Barrett's oesophagus]. 1610 Dec 22

Barrett's associated oesophageal adenocarcinoma (EAC) is one of the most rapidly increasing malignancies in Western countries. Because of its poor prognosis, management of this disease through screening of Barrett's oesophagus (BE) patients and identification of those with a high risk of developing an adenocarcinoma seems a promising approach. Early molecular markers of malignant transformation might contribute to such screening approaches. Gene promoter methylation analysis was performed on normal, pre-neoplastic, and neoplastic lesions from BE patients. All lesions of interest were sampled by microdissection from formalin-fixed paraffin-embedded tissue sections. We found that, in 27 adenocarcinomas, APC, TIMP3, TERT, CDKN2A, and SFRP1 promoters were methylated in 93%, 65%, 64%, 48%, and 91%, respectively; in contrast MLH1, RASSF1, RARB, CDH1, and FHIT promoters were methylated in less than 5% of the tumours. In BE mucosa from patients who had progressed to adenocarcinoma (12 samples), APC, TIMP3, and TERT promoters were hypermethylated in 100%, 91%, and 92% of cases, whereas in BE mucosa from patients who had not progressed (16 samples) methylation was found only in 36%, 23%, and 17%, respectively. Furthermore, the epigenetic profile of BE with and without EAC differed significantly with, respectively, 81% and 26% of the PCR samples showing promoter hypermethylation for APC, TIMP3, and TERT (p < 0.0001). Promoter methylation of CDKN2A was infrequently detected in BE samples, while SFRP1 methylation was observed in all samples. Our results suggest that promoter methylation profiling of BE using multiple target genes including APC, TIMP3, and TERT might be used as a predictive marker for increased EAC risk.
 ...
PMID:Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish Barrett's oesophagus patients at risk for malignant transformation. 1627 15

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate adenocarcinoma, but the frequency and timing of epigenetic changes found in prostate carcinogenesis has not been extensively documented. Thus, the promoters of three genes (APC, GSTP1, and RARbeta2) involved in prostate carcinogenesis were tested by quantitative methylation-specific PCR in tissue DNA from 30 prostate carcinomas, 128 high-grade PIN lesions, and 30 normal prostate tissue samples dissected from 30 radical prostatectomy specimens using laser capture microdissection. The percentage of methylated alleles (PMA) was calculated for each gene, and hierarchical cluster analysis was used to define the degree of similarity of epigenetic alterations among the various samples. We found that PMA values of APC and RARbeta2 were higher than those of GSTP1 in all three types of tissue samples and median PMA values for all three genes were higher in prostate cancer. By cluster analysis, 26 of 30 prostate carcinomas and 82 of 128 high-grade PIN lesions were grouped in the "high methylation" branch, whereas 24 of 30 normal prostate tissue samples were allocated in the "low methylation" branch. Although high-grade PIN lesions are epigenetically more similar to prostate carcinoma than to normal prostate tissue, paired prostate carcinoma and high-grade PIN lesions did not always segregate together. We concluded that APC and RARbeta2 hypermethylation is frequent in normal prostate tissue and the progressive enrichment in cells carrying methylated alleles observed in high-grade PIN and prostate carcinoma is consistent with clonal progression. Because GSTP1 promoter methylation is mainly observed in prostate carcinoma and some high-grade PIN lesions, it represents an important marker for the transition of in situ to invasive neoplasia.
 ...
PMID:Epigenetic heterogeneity of high-grade prostatic intraepithelial neoplasia: clues for clonal progression in prostate carcinogenesis. 1644 1

Genetic and epigenetic alterations are considered to play important roles in lung cancer. Recent studies showed that EGFR and K-RAS mutations exhibited a mutually exclusive pattern in adenocarcinoma of the lung, suggesting the presence of two independent oncogenic pathways. However, it is unknown how epigenetic alterations were involved in lung carcinogenesis mediated by EGFR or K-RAS mutation. In this study, we examined the relationship between genetic and epigenetic alterations in 164 cases of lung adenocarcinoma. Somatic mutations were determined by direct sequence of EGFR exons 18 to 21 and K-RAS codons 12 and 13. Methylation status of p16(INK4a), RASSF1A, APC, RARbeta, and CDH13, frequently methylated in lung cancer, was determined by methylation-specific PCR and the degree of methylation was defined as the methylation index. Multivariate analysis adjusted for age, sex, and smoking dose showed that the probability of having EGFR mutation was significantly lower among those with p16(INK4a) and CDH13 methylation than in those without [p16(INK4a): odds ratio (OR), 0.07; 95% confidence interval (95% CI), 0.02-0.33; CDH13: OR, 0.34; 95% CI, 0.15-0.77] and the methylation index was significantly lower in EGFR mutant cases than in wild type (OR, 0.70; 95% CI, 0.52-0.95). By contrast, K-RAS mutation was significantly higher in p16(INK4a) methylated cases than in unmethylated cases (OR, 4.93; 95% CI, 1.54-15.7) and the methylation index was higher in K-RAS mutant cases than in wild type with marginal significance (OR, 1.46; 95% CI, 0.95-2.25). Our results indicate the differences in the evolvement of epigenetic alterations between the EGFR- and K-RAS-mediated tumorigenesis and suggest the specific interaction of genetic and epigenetic changes in tumorigenesis of lung cancer.
 ...
PMID:Mutational and epigenetic evidence for independent pathways for lung adenocarcinomas arising in smokers and never smokers. 1645 91

Early (T1 stage) adenocarcinoma of the esophagus or gastroesophageal junction is a potentially curable disease. We analyzed the genomic spectra of 33 early neoplastic lesions after subdividing the tumors into six depths of invasion (T1-mucosal, m1-m3; T1-submucosal, sm1-sm3). Two subgroups were defined, T1m1-sm1 (n = 18) and T1sm2-sm3 (n = 15). The latter group is associated with frequent lymphatic spread and a high percentage of local and/or distant recurrence. Comparative genomic hybridization with a genomewide 3,500-element BAC-PAC array revealed a characteristic gastroesophageal adenocarcinoma pattern of changes, with losses on chromosome arms 4pq, 5q, 8p, 9p, 17p, and 18q and gains on 1q, 6p, 7pq, 11q, 15q, 17q, and 20pq. However, when the two groups were compared, the following BAC clones showed significantly more alterations in the T1sm2-sm3 group: RP11-534L20 (1q32.1) and RP11-175A4 (6p21.32), showing gains, and RP11-356F24, RP11-433L7, and RP11-241P12 (all at 8p), showing losses. Gain of RP11-534L20 (1q32.1) and loss of RP11-433L7 (8p22) were associated not only with a recurrence-free period (P = 0.0007 and 0.007, respectively), but also with regional lymphatic dissemination (P = 0.005 and 0.003, respectively). These DNA clones can be considered genomic markers for the aggressive behavior of early esophageal and gastroesophageal junction adenocarcinoma.
 ...
PMID:Genomic analysis of early adenocarcinoma of the esophagus or gastroesophageal junction: tumor progression is associated with alteration of 1q and 8p sequences. 1647 70

Small bowel adenocarcinoma (SB-AC) is a very rare tumor entity. Epigenetic alterations, including hypermethylation of DNA mismatch repair genes and tumor suppressor genes, seem to be important for carcinogenesis in tumors of the gastrointestinal tract, but have not yet been investigated in SB-AC. In the current study, the prevalence of hypermethylation in a panel of genes involved in gastrointestinal carcinogenesis (hMLH1, HPP1, p14(ARF), p16(INK4A), APC) was determined in a series of SB-AC. Paraffin-embedded tumor samples from 56 patients with SB-AC who underwent surgical resection between January 1985 and December 2003 were investigated for hypermethylation by means of methylation-specific real-time PCR, and compared with our findings in a previously investigated series of 50 gastric adenocarcinomas. In comparison with adenocarcinomas of the stomach, SB-AC revealed a significantly higher rate of hypermethylation of HPP1 (86% versus 54%, p = 0.0003), p16(INK4A) (32% versus 10%, p = 0.0006), and a significantly lower rate of hypermethylation of APC (48% versus 84%, p = 0.0001). Hypermethylation of hMLH1 and p14(ARF) was present in 23% and 9% of SB-AC, respectively. Locally advanced tumor categories (pT3/4) showed a higher rate of hypermethylation of HPP1 (90%) than did early tumor categories (pT1/2 categories, 40%; p = 0.0036). This was also reflected by the correlation between the HPP1 hypermethylation and high UICC stage (p = 0.02). No correlation was found between hypermethylation and other clinicopathologic parameters such as age, tumor grade and nodal status. Our findings suggest that hypermethylation of hMLH1, HPP1, p16(INK4A) and APC is frequent in primary adenocarcinomas of the small bowel. The differences in the hypermethylation spectrum of small bowel and stomach cancer indicate significant epigenetic differences between these tumors.
 ...
PMID:Hypermethylation of hMLH1, HPP1, p14(ARF), p16(INK4A) and APC in primary adenocarcinomas of the small bowel. 1661 16

Heterozygous germline DNA mismatch repair gene mutations are typically associated with HNPCC. Here we report the case of a proband whose father was known for familial adenomatous polyposis. The number of polyps (less than ten) was not typical of polyposis; therefore, the diagnosis of HNPCC was entertained. Microsatellite instability analyses were performed on peripheral blood and biopsy of a right-sided dysplastic adenoma. The tumor tissue showed high-grade instability, and a subsequent, immunohistochemistry showed that neither MSH2 nor MSH6 proteins were expressed in tumor cells. Prophylactic colectomy was performed, and an adenocarcinoma developing within the adenoma was diagnosed (pT1N0). Genomic DNA analysis revealed a novel mutation in MSH2 as a frameshift mutation in exon 7 (c.1191_1192dupG). Both parents of the proband were analysed for MSH2 and APC mutations, and in the father, a truncating mutation in exon 15 of APC was identified as del3471-3473GAGA. This mutation was found to be present in the proband. His mother was found to bear the MSH2 exon 7 mutation. At the follow-up, the proband was diagnosed with fundic, antral and duodenal adenomas (one fundic adenoma showed low-grade dysplasia). Several tubular rectal adenomas with low-grade dysplasia were excised. The patient later developed an intra-abdominal desmoid tumor.
 ...
PMID:Double frameshift mutations in APC and MSH2 in the same individual. 1583 12

Pathologic staging in colorectal adenocarcinoma (CA) is based on the concept that the timing of metastatic tumor spread is directly related to the depth of the primary tumor invasion. To evaluate the temporal sequence of CA metastasis, we performed microdissection mutational profiling at multiple microscopic sites of primary and metastatic CA specimens. Twenty-one cases of CA were selected from fixed-tissue archives. Primary tumors were microdissected at the deepest point of invasion. Comparative mutational profiling for different genomic loci [1p36(CCM = cutaneous malignant melanoma], 3p26(OGGI = 8 oxoguanine DNA glycosylase), 5q23 (APC, MCC = mutated in colorectal cancer), 9p21(p16/CDKN2A = cyclin-dependent kinase 2A), 10q23(PTEN = phosphatase and tensin homolog [mutated in multiple advanced cancers 11), 12p12(K-ras-2 point mutation), 17p13(TP53), 18q25(DCC= deleted in colorectal cancer) was carried out on each microdissected tissue target using microsatellite loss of heterozygosity determination or DNA sequencing. All primary and metastatic sites of CA manifested acquired mutational change in 18 to 91 per cent of the genomic markers. In 15/21 (71%) cases, metastatic sites lacked a specific allelic loss seen in the corresponding primary tumor, indicating that the metastasis occurred before maximal depth of primary invasion. This was further supported by discordant mutational profiles between primary and secondary tumors, requiring divergent clonal evolution. This is the first report describing the temporal sequence and significance of sequential mutational acquisition in clinical tissue specimens with potential implications for a new molecular pathology approach to classify human cancer.
 ...
PMID:Microdissection-based allelotyping: a novel technique to determine the temporal sequence and biological aggressiveness of colorectal cancer. 1671 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>