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)

We investigated the frequency and clinical significance of loss of heterozygosity (LOH) at the APC, MCC, and DCC tumor suppressor gene loci in 108 cases of resected non-small cell lung cancer (NSCLC). LOH at the APC/MCC gene cluster at chromosome 5q21 occurred frequently; it affected 29% of informative NSCLC cases and correlated with a significantly worse survival (P < 0.01). Furthermore, in the subtype most frequently affected (SCC), LOH at 5q not only correlated with a worse survival but also tumor involvement of the mediastinal and/or hilar nodes. In contrast, LOH at the DCC locus at chromosome 18q was far less frequent, occurring in 14% of NSCLC cases, and it was not associated with advanced stage or prognosis. These data suggest that LOH at 5q has a role in determining tumor progression and survival in NSCLC, and may prove to be a clinically useful prognostic indicator.
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PMID:Tumor progression and loss of heterozygosity at 5q and 18q in non-small cell lung cancer. 781 47

Tumor suppressor genes APC, RB1, and DCC, as well as genes localized to 3p and 11q, have been implicated in the development of a number of human tumors. To determine whether allelic deletions occur at these loci in squamous cell carcinomas (SSCs) of the head and neck, 25 primary, 1 metastatic, and 3 recurrent tumors, along with the corresponding constitutional tissues, were analyzed by using a battery of polymorphic DNA markers. For two primary tumors, we also analyzed subsequent metastatic tumors of the lung. Polymerase chain reaction-based restriction fragment length polymorphism studies demonstrated loss of heterozygosity for the APC gene in 2 of 12 (17%), the RB1 gene in 5 of 22 (23%), and the DCC gene in 5 of 13 (38%) informative cases. Alleles on chromosomes 3p, 11q13, and 18q21.1 were lost in 7 of 20 (35%), 9 of 23 (39%), and 4 of 17 (24%) informative cases, respectively. A breakpoint was identified within the chromosomal region 3p13-21.2 in a SCC of the tongue. Breakpoints within 11q13 were identified in 2 additional tumors. Thus, allelic deletions of DCC, 3p, and 11q13 appear to be common in head and neck cancers, suggesting that these genes play a critical and complex role in the development of these tumors. Furthermore, the present study provides definitive evidence for a tumor suppressor gene at chromosome band 11q13 and localizes this gene to the INT2-D11S533 interval for future cloning and sequencing.
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PMID:Loss of heterozygosity in squamous cell carcinomas of the head and neck defines a tumor suppressor gene region on 11q13. 966 6

We determined the frequency of loss of heterozygosity (LOH) at chromosome 5q21-22 (adenomatous polyposis gene region) in oral SCC from 49 patients using PCR-based assays. Of 43 informative (heterozygous) tumors, 41.9% [95% confidence interval (CI)=27.0, 57.9] contained LOH at 5q21-22. LOH at 5q21-22 was strongly associated with stage at diagnosis: 100%, (3/3), 50% (13/26), and 14% (2/14) of tumors from patients with distant metastases, regional spread, and localized disease, respectively, contained this genetic alteration (P=0.01). There were no statistically significant associations between LOH at 5q21-22 and other patient or tumor characteristics, but LOH was more commonly found in the tumors of heavy smokers, infrequent alcohol consumers, and in tumors containing either p53 mutations or HPV-DNA. In univariate analyses, LOH at 5q21-22 was associated with poor prognosis (hazard ratio=1.8, 95%, CI 0.8, 4.5); this relationship did not persist after adjustment for stage of disease (hazard ratio=1.1, 95% CI=0.4, 3.1). These data provide further evidence that inactivation of the APC gene and/or other genes at 5q21-22 is common and may be involved in the development and/or progression of oral SCC. Larger studies are needed to determine whether LOH at 5q21-22 is linked to known oral SCC etiologic factors and/or the prognosis of oral SCC patients, as well as to genetic instability at other loci involved in these malignancies.
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PMID:Loss of heterozygosity at 5q21-22 (adenomatous polyposis coli gene region) in oral squamous cell carcinoma is common and correlated with advanced disease. 972 66

Lung cancer is the leading cause of death in both women and men in the United States and many European countries. Molecular cytogenetic and LOH analyses of non-small cell lung cancer have shown somatic genetic alterations in a variety of chromosomes, such as 1p, 3p, 5q, 8p, 9p, 11p, 11q and 17p. Allelic deletions of the known tumor suppressor gene APC at 5q21 are frequently observed in advanced stages of lung cancer and have been correlated with poor prognosis in previous reports. We investigated 33 cases of NSCL for LOH at 5q21: 22 squamous cell and 11 adenocarcinomas. Normal and tumor cells were microdissected from paraffin embedded tissues and PCR amplification was performed utilising the specific markers D5S299 and D5S346 at 5q21 and PYGM at 11q13, respectively. Clinicopathological data, survival and recurrence rates were obtained in all cases. We detected LOH at 5q21 in 4/9 (44%) informative adenocarcinomas and in 13/16 (81%) informative SCC. LOH was frequent in early stages (12/15 stage I cases) and did not correlate with recurrence or poor survival. Our results show that LOH at 5q21 is more frequent in squamous cell carcinomas than in adenocarcinomas, is frequent in early stages of the disease, and does not have prognostic significance.
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PMID:LOH at the APC/MCC gene (5Q21) is frequent in early stages of non-small cell lung cancer. 1054 31

INTRODUCTION: This study examined the contribution of promoter hypermethylation to the pathogenesis of respiratory papillomatosis (RP), including recurrences (RRP) and progression to squamous cell carcinoma (SSC). MATERIALS AND METHODS: A retrospective cohort of 25 laryngeal papilloma cases included 21 RRP, two of which progressed to SCC. Aberrant methylation status was determined using the multi-gene (22 tumor suppressor genes) methylation-specific multiplex ligation-dependent probe amplification assay and confirmed using methylation specific PCR. RESULTS: Twenty genes had altered DNA methylation in 22 of 25 cases. Aberrant methylation of CDKN2B and TIMP3 was most frequent. Promoter hypermethylation of BRCA2, APC, CDKN2A and CDKN2B was detected in 2 RRP cases with subsequent progression to SCC. Of the 25 cases, 22 were positive for HPV-6, 2 for HPV-11 and 1 for HPV-16 and 33. CONCLUSIONS: Consistent aberrant methylation of multiple tumor suppressor genes contributes to the pathogenesis of laryngeal papillomas. Persistent aberrant DNA methylation events in 2 RRP cases that progressed to cancer indicate an epigenetic monoclonal progression continuum to SCC.
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PMID:Consistent DNA hypermethylation patterns in laryngeal papillomas. 2160 83