CpG Island Methylation According to the Histologic Patterns of Early Gastric Adenocarcinoma
최준정, 조미연, 정소영, Jan Khalilullah Mia, 김현수,
소속 상세정보
최준정 ( Choi Jun-Jeong )
Yonsei University Wonju College of Medicine Department of Pathology
조미연 ( Cho Mee-Yon )
Yonsei University Wonju College of Medicine Department of Pathology
정소영 ( Jung So-Young )
Yonsei University Wonju College of Medicine Department of Pathology
( Jan Khalilullah Mia )
Yonsei University Wonju College of Medicine Department of Pathology
김현수 ( Kim Hyun-Soo )
Yonsei University Wonju College of Medicine Department of Internal Medicine
KMID : 0357920110450050469
Abstract
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 hypome-thylation 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.
키워드
Adenoma;CpG Islands;DNA methylation;Dysplasia;Stomach
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