Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers
<p>Abstract</p> <p>Background</p> <p>Epidemiological studies indicate that some characteristics of lung cancer among never-smokers significantly differ from those of smokers. Aberrant promoter methylation and mutations in some oncogenes and tumor suppressor genes are fr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2007-05-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/7/74 |
| _version_ | 1811250179951558656 |
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| author | Weissfeld Joel L Siegfried Jill M Gao Weimin Liu Yang Luketich James D Keohavong Phouthone |
| author_facet | Weissfeld Joel L Siegfried Jill M Gao Weimin Liu Yang Luketich James D Keohavong Phouthone |
| author_sort | Weissfeld Joel L |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Epidemiological studies indicate that some characteristics of lung cancer among never-smokers significantly differ from those of smokers. Aberrant promoter methylation and mutations in some oncogenes and tumor suppressor genes are frequent in lung tumors from smokers but rare in those from never-smokers. In this study, we analyzed promoter methylation in the <it>ras-association domain isoform A (RASSF1A) </it>and the <it>death-associated protein kinase (DAPK) </it>genes in lung tumors from patients with primarily non-small cell lung cancer (NSCLC) from the Western Pennsylvania region. We compare the results with the smoking status of the patients and the mutation status of the K-<it>ras</it>, <it>p53</it>, and <it>EGFR </it>genes determined previously on these same lung tumors.</p> <p>Methods</p> <p>Promoter methylation of the <it>RASSF1A </it>and <it>DAPK </it>genes was analyzed by using a modified two-stage methylation-specific PCR. Data on mutations of K-<it>ras</it>, <it>p53</it>, and <it>EGFR </it>were obtained from our previous studies.</p> <p>Results</p> <p>The <it>RASSF1A </it>gene promoter methylation was found in tumors from 46.7% (57/122) of the patients and was not significantly different between smokers and never-smokers, but was associated significantly in multiple variable analysis with tumor histology (p = 0.031) and marginally with tumor stage (p = 0.063). The <it>DAPK </it>gene promoter methylation frequency in these tumors was 32.8% (40/122) and did not differ according to the patients' smoking status, tumor histology, or tumor stage. Multivariate analysis adjusted for age, gender, smoking status, tumor histology and stage showed that the frequency of promoter methylation of the <it>RASSF1A </it>or <it>DAPK </it>genes did not correlate with the frequency of mutations of the K<it>-ras, p53</it>, and <it>EGFR </it>gene.</p> <p>Conclusion</p> <p>Our results showed that <it>RASSF1A </it>and <it>DAPK </it>genes' promoter methylation occurred frequently in lung tumors, although the prevalence of this alteration in these genes was not associated with the smoking status of the patients or the occurrence of mutations in the K-<it>ras</it>, <it>p53 </it>and <it>EGFR </it>genes, suggesting each of these events may represent independent event in non-small lung tumorigenesis.</p> |
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| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T15:59:25Z |
| publishDate | 2007-05-01 |
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| series | BMC Cancer |
| spelling | doaj.art-801736b4c65849f28a01148b5ba320412022-12-22T03:26:14ZengBMCBMC Cancer1471-24072007-05-01717410.1186/1471-2407-7-74Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokersWeissfeld Joel LSiegfried Jill MGao WeiminLiu YangLuketich James DKeohavong Phouthone<p>Abstract</p> <p>Background</p> <p>Epidemiological studies indicate that some characteristics of lung cancer among never-smokers significantly differ from those of smokers. Aberrant promoter methylation and mutations in some oncogenes and tumor suppressor genes are frequent in lung tumors from smokers but rare in those from never-smokers. In this study, we analyzed promoter methylation in the <it>ras-association domain isoform A (RASSF1A) </it>and the <it>death-associated protein kinase (DAPK) </it>genes in lung tumors from patients with primarily non-small cell lung cancer (NSCLC) from the Western Pennsylvania region. We compare the results with the smoking status of the patients and the mutation status of the K-<it>ras</it>, <it>p53</it>, and <it>EGFR </it>genes determined previously on these same lung tumors.</p> <p>Methods</p> <p>Promoter methylation of the <it>RASSF1A </it>and <it>DAPK </it>genes was analyzed by using a modified two-stage methylation-specific PCR. Data on mutations of K-<it>ras</it>, <it>p53</it>, and <it>EGFR </it>were obtained from our previous studies.</p> <p>Results</p> <p>The <it>RASSF1A </it>gene promoter methylation was found in tumors from 46.7% (57/122) of the patients and was not significantly different between smokers and never-smokers, but was associated significantly in multiple variable analysis with tumor histology (p = 0.031) and marginally with tumor stage (p = 0.063). The <it>DAPK </it>gene promoter methylation frequency in these tumors was 32.8% (40/122) and did not differ according to the patients' smoking status, tumor histology, or tumor stage. Multivariate analysis adjusted for age, gender, smoking status, tumor histology and stage showed that the frequency of promoter methylation of the <it>RASSF1A </it>or <it>DAPK </it>genes did not correlate with the frequency of mutations of the K<it>-ras, p53</it>, and <it>EGFR </it>gene.</p> <p>Conclusion</p> <p>Our results showed that <it>RASSF1A </it>and <it>DAPK </it>genes' promoter methylation occurred frequently in lung tumors, although the prevalence of this alteration in these genes was not associated with the smoking status of the patients or the occurrence of mutations in the K-<it>ras</it>, <it>p53 </it>and <it>EGFR </it>genes, suggesting each of these events may represent independent event in non-small lung tumorigenesis.</p>http://www.biomedcentral.com/1471-2407/7/74 |
| spellingShingle | Weissfeld Joel L Siegfried Jill M Gao Weimin Liu Yang Luketich James D Keohavong Phouthone Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers BMC Cancer |
| title | Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers |
| title_full | Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers |
| title_fullStr | Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers |
| title_full_unstemmed | Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers |
| title_short | Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers |
| title_sort | promoter methylation of rassf1a and dapk and mutations of k ras p53 and egfr in lung tumors from smokers and never smokers |
| url | http://www.biomedcentral.com/1471-2407/7/74 |
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