Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current multistep carcinogenesis models of colon cancer do not fully capture the genetic heterogeneity of the disease, which is additionally complicated by the presence of passenger and driver genetic alterations. The aim of this study was to select in the context of this significant heterogeneity additional genes functionally related to colon cancer development. High-throughput copy number and gene expression data of 36 microsatellite stable sporadic colon cancers resected from patients of a single institution characterized for mutations in APC, KRAS, TP53 and loss of 18q were analyzed. Genes whose expression correlated with the underlying copy number pattern were selected, and their association with the above listed mutations and overall survival was evaluated. Gain of 20q was strongly associated with TP53 mutation, and overall survival with alterations on 7p, 8p, 13q, 18q, and 20q. An association with 18q loss and gain of 8q24 was also observed. New candidate genes with a potential role in colon cancer are PLCG1 on 20q, DBC1 on 8q21, and NDGR1 on 8p24. In addition, an unexpected pattern of loss and mutability was found in the region upstream of the KRAS gene. By integrating copy number alterations with gene expression and mutations in colon cancer associated genes, we have developed a strategy that identifies previously known molecular features and additional players in the molecular landscape of colon cancer.
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PMID:Integrative approach for prioritizing cancer genes in sporadic colon cancer. 1967 74

The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We also analyzed urine samples from 33 patients with noncancerous urinary lesions. A total of 95 oncogenic mutations and 189 hypermethylation events were detected in the 105 tumor biopsies. The total panel of markers provided a sensitivity of 93%, whereas mutation and methylation markers alone provided sensitivities of 72% and 70%, respectively. In urine samples, the sensitivity was 70% for all markers, 50% for mutation markers and 52% for methylation markers. FGFR3 mutations occurred more frequently in tumors with no methylation events than in tumors with one or more methylation events (78% vs. 33%; p < 0.0001). FGFR3 mutation in combination with three methylation markers (APC, RASSF1A and SFRP2) provided a sensitivity of 90% in tumors and 62% in urine with 100% specificity. These results suggest an inverse correlation between FGFR3 mutations and hypermethylation events, which may be used to improve noninvasive, DNA-based detection of bladder cancer.
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PMID:Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events. 2082 3