- The Relationship between the Methylenetetrahydrofolate Reductase Genotypes and the Methylation Status of the CpG Island Loci, LINE-1 and Alu in Prostate Adenocarcinoma.
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Jung Ho Kim, Nam Yun Cho, Baek Hee Kim, Wook Youn Kim, Bo Sung Kim, Kyung Chul Moon, Gyeong Hoon Kang
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Korean J Pathol. 2009;43(1):26-35.
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DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.26
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 Abstract
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- BACKGROUND
Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR), in association with the influence of MTHFR upon DNA methylation, may cause differences of the methylation profile of cancer. Thus, we investigated the relationship between the methylation status of prostate adenocarcinoma and the genetic polymorphism of MTHFR.
METHODS
We examined 179 cases of prostate adenocarcinoma for determining the genotypes of MTHFR 677 and 1298, the methylation status of 16 CpG island loci and the methylation levels of the LINE-1 and Alu repeats with using polymerase chain reaction/restriction fragment length polymorphism, methylation-specific polymerase chain reaction and combined bisulphite restriction analysis, respectively.
RESULTS
There was a higher proportion of the CT genotype of MTHFR 677 in the prostate adenocarcinoma than that in the normal control. The TT genotype of MTHFR 677 showed the highest frequency of methylation in six out of nine major CpG island loci, and these were which were frequently hypermethylated in prostate adenocarcinoma. The CT type showed the lowest methylation levels of LINE-1 and Alu among the MTHFR 677 genotypes. Interestingly, the CC type of MTHFR 1298 demonstrated favorable prognostic factors.
CONCLUSIONS
Our study is the first to examine the methylation profile of prostate adenocarcinoma according to the MTHFR genotypes. The differences of the cancer risk, the genomic hypomethylation and the prognosis between the MTHFR genotypes in prostate adenocarcinoma should be further explored.
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Citations
Citations to this article as recorded by  - Association Between MTHFR 1298A>C Polymorphism and Spontaneous Abortion with Fetal Chromosomal Aneuploidy
Shin Young Kim, So Yeon Park, Ji Won Choi, Do Jin Kim, Shin Yeong Lee, Ji Hyae Lim, Jung Yeol Han, Hyun Mee Ryu, Min Hyoung Kim
American Journal of Reproductive Immunology.2011; 66(4): 252. CrossRef - Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences
Pornrutsami Jintaridth, Apiwat Mutirangura
Physiological Genomics.2010; 41(2): 194. CrossRef
- The Prognostic Implications of the Histologic Subtype and the Expression of Phosphorylated ERK 1/2 in Papillary Renal Cell Carcinoma.
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Bo Sung Kim, Dong Il Kim, Tae Hoon Kang, Eun Shin, Kyung Chul Moon
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Korean J Pathol. 2008;42(4):215-222.
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Abstract
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- BACKGROUND
The authors of this study wanted to confirm the prognostic implication of the histologic subtype; further, we wanted to explore the expression of phosphorylated extracellular signal-regulated kinase 1/2 (pERK) in papillary renal cell carcinoma (PRCC) and determine its clinicopathologic and prognostic significance.
METHODS
A total of 45 patients who underwent nephrectomy for PRCC were enrolled in this study. The hematoxylin and eosin slides were reviewed and pERK immunohistochemistry was performed.
RESULTS
Type 2 PRCC was significantly correlated with a larger tumor size (p=0.030), a higher nuclear grade (p<0.001), a more advanced tumor stage (p=0.041) and more frequent distant metastasis (p=0.019). The tumors were pERK-low (0 and 1+) in 30 cases (66.7%) and pERK-high (2+) in 15 cases (33.3%). The pERK-high PRCC was significantly associated with a smaller tumor size (p=0.001) and an earlier tumor stage (p=0.004). On the univariate analysis, the histologic subtype, the TNM stage and the pERK status were significantly associated with progression-free survival (PFS). Multivariate analysis showed that the histologic subtype (hazard ratio 22.81, p=0.042) and the TNM stage (hazard ratio 23.48, p=0.009) were independent prognostic factors for PFS.
CONCLUSIONS
Type 2 PRCC, together with the TNM stage, was identified as one of independent poor prognostic factors for PFS. The pERK status was a prognostic factor for PFS on the univariate analysis, but not on the multivariate analysis.
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