Journal of Pathology and Translational Medicine

Original Articles

CpG Island Methylation According to the Histologic Patterns of Early Gastric Adenocarcinoma.: Junjeong Choi, Mee Yon Cho, So Young Jung, Khalilullah Mia Jan, Hyun Soo Kim; Korean J Pathol. 2011;45(5):469-476.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.469

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BACKGROUND
Although the importance of aberrant DNA methylation in the development of gastric adenocarcinoma has been described, the mechanism of pathogenesis has not been revealed yet. We quantitatively analyzed methylation of four CpG islands and one repetitive DNA element, according to the histologic features of adenocarcinoma with precursor lesions.
METHODS
We divided the cases as adenocarcinoma with intestinal type precursors (type A, n=19 cases) and adenocarcinoma with diffuse type precursors (type B, n=19 cases). We micro-dissected tumor cells and matched non-neoplastic gastric mucosa from the hematoxylin and eosin-stained slides.
RESULTS
A total of 20 CpG sites of long interspersed nucleotide element-1 (LINE1), RAR-related orphan receptor alpha (RORA), Kruppel-like factor 7 (KLF7), mutL homolog 1 (MLH1), MINT25, and CD133 were analyzed. Methylation was determined by bisulfate-pyro-sequencing, and hypomethylation of LINE1 and CD133 was noted in the tumors, compared to the levels in the non-neoplastic gastric mucosa (p=0.014 and p=0.015, respectively). A statistically different methylation pattern of CpG sites at CD133 and KLF7 was noted only in type B lesions, compared to that in matched non-neoplastic gastric mucosa (p=0.027 and p=0.043, respectively).
CONCLUSIONS
Given that aberrant methylation occurs in a relatively early phase of carcinogenesis, different patterns of methylation may determine the carcinoma phenotype. However, further large-scale study is required to clarify the significance of this difference.

Citations

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Molecular function of Krüppel-like factor 7 in biology
Yi Mao, Yuechan Chen, Zhiwei Zhang
Acta Biochimica et Biophysica Sinica.2023; 55(5): 713. CrossRef
DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis
YOSEP CHONG, KHALILULLAH MIA-JAN, HOON RYU, JAMSHID ABDUL-GHAFAR, JIJGEE MUNKHDELGER, SAYAMAA LKHAGVADORJ, SO YOUNG JUNG, MIRA LEE, SUN-YOUNG JI, EUNHEE CHOI, MEE-YON CHO
Oncology Reports.2014; 31(6): 2535. CrossRef

The Relationship between the Methylenetetrahydrofolate Reductase Genotypes and the Methylation Status of the CpG Island Loci, LINE-1 and Alu in Prostate Adenocarcinoma.: Jung Ho Kim, Nam Yun Cho, Baek Hee Kim, Wook Youn Kim, Bo Sung Kim, Kyung Chul Moon, Gyeong Hoon Kang; Korean J Pathol. 2009;43(1):26-35.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.26

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Abstract PDF

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.

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

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