胃癌の発生・進展と遺伝子変化―病理形態学の立場から

Genetic Changes in Development of Gastric Carcinoma

要旨　胃癌における遺伝子変化の解析はまだまだ発展途上にあるが，現時点での研究成果を分化型胃癌と未分化型胃癌に分けてまとめてみた．両型に共通にみられる変化としては，c-met遺伝子の増幅，APC遺伝子やp53遺伝子の変異などがある．分化型に比較的特異な変化としては，c-erbB-2遺伝子の増幅，c-met遺伝子のLOHなどがあり，未分化型にみられる変化としては，K-sam遺伝子の増幅，遺伝子不安定性をみるmicrosatellite markerの変異の増加などがある．このほか，種々の対立遺伝子の欠失（LOH）についても触れた．また，前癌病変であるいわゆるATP（扁平腺腫）における変化としては，APC遺伝子の変異の頻度が高い．また，多重癌発生の高危険状態を知るための手段として，腫瘍からのDNAについてmicrosatellite markerを用いてRER（replication error）を検索することが有用であることを示した．

　The still rapidly expanding knowledge of genetic changes in gastric carcinogenesis was summarized. When gastric carcinomas are divided into differentiated type (DCA) and undifferentiated type (UCA), amplification of c-met gene, and mutations of APC gene (well or moderately differentiated adenocarcinoma and signet-ring cell carcinoma) and p53 gene are changes common to both types. Specifics for DCA are mutation of ras gene (though rare), amplification of c-erbB-2 gene and loss of heterozygosity (LOH) of c-met gene. On the other hand for UCA, amplification of K-sam, and replication error (RER) in microsatellite marker DNAs is supposed to reflect genetic instability (poorly differentiated carcinoma). LOHs on several chromosomal arms were also referred to. In so-called ATP or flat adenoma, mutation of APC gene is frequent compared to other genetic alterations. It is suggested that it is useful to examine RER in microsatellite marker DNAs from the tumor for the screening of patients at risk of developing of multiple cancer.