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Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival.
Oncogene. 2001 Jun 14; 20(27):3528-32.O

Abstract

Methylation of 5' CpG islands in promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of this study was to determine whether hypermethylation of the adenomatous polyposis coli (APC) gene promoter occurs in primary non-small cell lung cancer (NSCLC), and whether hypermethylated APC has any relationship with survival. APC promoter 1A methylation was determined in normal and corresponding tumor tissue from 91 NSCLC patients and in a control group of 10 patients without cancer, using a quantitative fluorogenic real-time PCR (Taqman) system. APC promoter methylation was detectable in 86 (95%) of 91 tumor samples, but also in 80 (88%) of 91 normal samples of NSCLC patients, and in only two (20%) of 10 normal lung tissues of the control group. The median level of APC promoter methylation was 4.75 in tumor compared to 1.57 in normal lung tissue (P<0.001). Patients with low methylation status showed significantly longer survival than did patients with high methylation status (P=0.041). In a multivariate analysis of prognostic factors, APC methylation was a significant independent prognostic factor (P=0.044), as were pT (P=0.050) and pN (P<0.001) classifications. This investigation shows that APC gene promoter methylation occurs in the majority of primary NSCLCs. High APC promoter methylation is significantly associated with inferior survival, showing promise as a biomarker of biologically aggressive disease in NSCLC.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, CA 90033, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11429699

Citation

Brabender, J, et al. "Adenomatous Polyposis Coli Gene Promoter Hypermethylation in Non-small Cell Lung Cancer Is Associated With Survival." Oncogene, vol. 20, no. 27, 2001, pp. 3528-32.
Brabender J, Usadel H, Danenberg KD, et al. Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival. Oncogene. 2001;20(27):3528-32.
Brabender, J., Usadel, H., Danenberg, K. D., Metzger, R., Schneider, P. M., Lord, R. V., Wickramasinghe, K., Lum, C. E., Park, J., Salonga, D., Singer, J., Sidransky, D., Hölscher, A. H., Meltzer, S. J., & Danenberg, P. V. (2001). Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival. Oncogene, 20(27), 3528-32.
Brabender J, et al. Adenomatous Polyposis Coli Gene Promoter Hypermethylation in Non-small Cell Lung Cancer Is Associated With Survival. Oncogene. 2001 Jun 14;20(27):3528-32. PubMed PMID: 11429699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival. AU - Brabender,J, AU - Usadel,H, AU - Danenberg,K D, AU - Metzger,R, AU - Schneider,P M, AU - Lord,R V, AU - Wickramasinghe,K, AU - Lum,C E, AU - Park,J, AU - Salonga,D, AU - Singer,J, AU - Sidransky,D, AU - Hölscher,A H, AU - Meltzer,S J, AU - Danenberg,P V, PY - 2001/01/18/received PY - 2001/01/20/revised PY - 2001/03/07/accepted PY - 2001/6/29/pubmed PY - 2001/7/20/medline PY - 2001/6/29/entrez SP - 3528 EP - 32 JF - Oncogene JO - Oncogene VL - 20 IS - 27 N2 - Methylation of 5' CpG islands in promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of this study was to determine whether hypermethylation of the adenomatous polyposis coli (APC) gene promoter occurs in primary non-small cell lung cancer (NSCLC), and whether hypermethylated APC has any relationship with survival. APC promoter 1A methylation was determined in normal and corresponding tumor tissue from 91 NSCLC patients and in a control group of 10 patients without cancer, using a quantitative fluorogenic real-time PCR (Taqman) system. APC promoter methylation was detectable in 86 (95%) of 91 tumor samples, but also in 80 (88%) of 91 normal samples of NSCLC patients, and in only two (20%) of 10 normal lung tissues of the control group. The median level of APC promoter methylation was 4.75 in tumor compared to 1.57 in normal lung tissue (P<0.001). Patients with low methylation status showed significantly longer survival than did patients with high methylation status (P=0.041). In a multivariate analysis of prognostic factors, APC methylation was a significant independent prognostic factor (P=0.044), as were pT (P=0.050) and pN (P<0.001) classifications. This investigation shows that APC gene promoter methylation occurs in the majority of primary NSCLCs. High APC promoter methylation is significantly associated with inferior survival, showing promise as a biomarker of biologically aggressive disease in NSCLC. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11429699/Adenomatous_polyposis_coli_gene_promoter_hypermethylation_in_non_small_cell_lung_cancer_is_associated_with_survival_ L2 - https://doi.org/10.1038/sj.onc.1204455 DB - PRIME DP - Unbound Medicine ER -