| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
APC, E-cadherin gene mutation and methylation and hMLH1 gene methylation, and mucus phenotype of colorectal serrated adenoma (SA) were investigated and compared with those of tubular adenoma (TA).
1. APC : Both mutation (exon 1 to 7) and methylation rate of SA [3% (1/34), 19.2% (5/23)] were significantly lower that those of TA [40% (4/10), 90% (9/10)] (p<0.005).
2. E-cadherin : No significant difference was found in mutation (exon 6-9) and methylation rate between SA [6% (2/34), 68% (23/24)] and TA [0% (0/10), 50% (5/10)]. Mutation found in SA was identical with that found in gastric carcinoma with gastric mucus phenotype (18-base pair deletion of codon 418 to 423).
3. hMLH1: methylation was found in 88% (30/34) of SA.
4. Mucus phenotype: Although there was no significant difference in MUC5AC expression between SA[93.5% (29/31)] and TA[90.5% (19/21)], MUC6 was highly expressed in SA[71% (22/31)] than TA[14.3% (3/21)] (p<0.0001).
5. Conclusion and Discussion : APC and E-cadherin alterations would not play a role in the development of SA. Role of abnormality in hMLH1 remained to be elucidated. Expression of MUC6 (gastric pyloric type core protein) was the characteristic phenotype of SA. Identical mutational pattern seen in SA and gastric carcinoma with gastric phenotype suggested a possibility that neoplasia with gastric mucus phenotype, regardless of organ, may be involved in common genetic alterations.
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