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Promoter Methylation of CDKN2A, RARβ, and RASSF1A in Non-Small Cell Lung Carcinoma: Quantitative Evaluation Using Pyrosequencing.

Lee JU, Sul HJ, Son JW - Tuberc Respir Dis (Seoul) (2012)

Bottom Line: Hyperrmethylation of CDKN2A was significantly associated with p16(INK4A) immunoexpression loss (p=0.045).With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16(INK4A) immunoexpression (p=0.016).We showed a significant correlation between CDKN2A hypermethylation and p16(INK4A) immunoexpression loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, St. Mary's Hospital, The Catholic University of Korea School of Medicine, Daejeon, Korea.

ABSTRACT

Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, RARβ, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs.

Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, RARβ, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of p16(INK4A) immunoexpression.

Results: Hypermethylation of CDKN2A, RARβ, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with p16(INK4A) immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16(INK4A) immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed p16(INK4A) immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another.

Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and p16(INK4A) immunoexpression loss.

No MeSH data available.


Related in: MedlinePlus

Detection of CDKN2A, RARβ, RASSF1A promoter hypermethylation in non-small cell lung cancer. Pyrograms illustrating the 6 CpGs in the CDKN2A promoter, the 5 CpGs in the RARβ promoter, and 6 CpGs in the RASSF1A promoter.
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Figure 1: Detection of CDKN2A, RARβ, RASSF1A promoter hypermethylation in non-small cell lung cancer. Pyrograms illustrating the 6 CpGs in the CDKN2A promoter, the 5 CpGs in the RARβ promoter, and 6 CpGs in the RASSF1A promoter.

Mentions: We evaluated the methylation status of the CDKN2A, RARβ, and RASSF1A gene promoters in 13 lung cancer tissue samples and 13 corresponding normal lung tissue samples by using pyrosequencing (Table 3, Figure 1). The mean methylation levels of normal lung tissues were 1.79, 5.07, and 3.15 and of tumor tissues were 12.16, 20.9, and 8.53 for CDKN2A, RARβ, and RASSF1A, respectively. On the basis of these results, we defined promoter hypermethylation in a tumor tissue as a 2-fold increase in normal tissue5, i.e., 3.58, 10.14, and 6.30 in CDKN2A, RARβ, and RASSF1A, respectively. We further analyzed an additional 40 tumor tissues by using pyrosequencing (Table 4).


Promoter Methylation of CDKN2A, RARβ, and RASSF1A in Non-Small Cell Lung Carcinoma: Quantitative Evaluation Using Pyrosequencing.

Lee JU, Sul HJ, Son JW - Tuberc Respir Dis (Seoul) (2012)

Detection of CDKN2A, RARβ, RASSF1A promoter hypermethylation in non-small cell lung cancer. Pyrograms illustrating the 6 CpGs in the CDKN2A promoter, the 5 CpGs in the RARβ promoter, and 6 CpGs in the RASSF1A promoter.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3475475&req=5

Figure 1: Detection of CDKN2A, RARβ, RASSF1A promoter hypermethylation in non-small cell lung cancer. Pyrograms illustrating the 6 CpGs in the CDKN2A promoter, the 5 CpGs in the RARβ promoter, and 6 CpGs in the RASSF1A promoter.
Mentions: We evaluated the methylation status of the CDKN2A, RARβ, and RASSF1A gene promoters in 13 lung cancer tissue samples and 13 corresponding normal lung tissue samples by using pyrosequencing (Table 3, Figure 1). The mean methylation levels of normal lung tissues were 1.79, 5.07, and 3.15 and of tumor tissues were 12.16, 20.9, and 8.53 for CDKN2A, RARβ, and RASSF1A, respectively. On the basis of these results, we defined promoter hypermethylation in a tumor tissue as a 2-fold increase in normal tissue5, i.e., 3.58, 10.14, and 6.30 in CDKN2A, RARβ, and RASSF1A, respectively. We further analyzed an additional 40 tumor tissues by using pyrosequencing (Table 4).

Bottom Line: Hyperrmethylation of CDKN2A was significantly associated with p16(INK4A) immunoexpression loss (p=0.045).With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16(INK4A) immunoexpression (p=0.016).We showed a significant correlation between CDKN2A hypermethylation and p16(INK4A) immunoexpression loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, St. Mary's Hospital, The Catholic University of Korea School of Medicine, Daejeon, Korea.

ABSTRACT

Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, RARβ, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs.

Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, RARβ, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of p16(INK4A) immunoexpression.

Results: Hypermethylation of CDKN2A, RARβ, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with p16(INK4A) immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16(INK4A) immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed p16(INK4A) immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another.

Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and p16(INK4A) immunoexpression loss.

No MeSH data available.


Related in: MedlinePlus