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要旨 DCC遺伝子コドン201(Arg/Gly)の多様性を表面型腫瘍37例を対象とし,隆起型腫瘍81例,進行癌54例と比較した.腫瘍高が正常粘膜以下のものを表面型とした.末梢血・正常粘膜に201Glyフェノタイプを認めたものは,表面型ではlow grade dysplasia(low)67%,high grade dysplasia(high)64%,sm carcinoma64%と異型度にかかわらず高率であった.隆起型ではlow20%,high48%,sm carcinoma50%,進行癌では54%,対照は17%であった.末梢血・正常粘膜に201Arg/Glyヘテロ接合体を有する例で,腫瘍部に片対立遺伝子の欠失を認めた6例のうち5例は201Argが欠失し,201Glyが残存していた.以上から,DCC遺伝子コドン201Glyフェノタイプは表面型腫瘍にも密接に関与していることが示唆された.
Codon 201Arg/Gly polymorphism in the DCC (deleted in colorectal carcinoma) gene was analyzed in 37 flat type colorectal tumors and compared with that of 81 polypoid type tumors and 54 advanced carcinomas. The flat type was defined microscopically as one whose height was less than that of the surrounding normal mucosa, and others were included in the polypoid type. The phenotypic frequencies of the codon 201Gly in flat type tumors were 67% (6/9), 64% (9/14), 64% (9/14) in low grade dysplasia (low), high grade dysplasia (high), carcinoma invading the submucosa (sm carcinoma), respectively. There were high frequencies of the codon 201Gly phenotype in flat type tumors as well as in polypoid type high 48% (16/33), sm carcinoma 50% (14/28) and advanced carcinoma 54% (29/54), but flat type tumors showed significantly higher frequencies of codon 201Gly phenotype than polypoid type low 20% (4/20) and controls (who had neither colorectal tumor nor a family history of colon cancer) 17% (5/30) . The codon 201 phenotype in the colorectal tumor tissues did not differ from that in the surrounding normal mucosa or in peripheral blood leukocytes, except that loss of heterozeigosity (LOH) occurred in the six cases with carcinoma. Five of them with LOH showed the codon 201Gly allele deletion and one patient showed the codon 201Gly allele deletion. These results suggest that the codon 201Gly phenotype in the DCC gene is not only a useful genetic marker for malignant colorectal tumors but that it is closely related to flat type colorectal tumors.
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