腺管腺癌に由来する未分化型胃癌の系譜解析

抄録

Using comparative genomic hybridization (CGH)-based lineage analyses, we have recently demonstrated that there are two genetic lineages in poorly differentiated adenocarcinoma (POR) with tubular component (TC) in the stomach: one derived form signet ring cell carcinoma and the other from tubular adenocarcinoma (TUB). It still remains open whether the POR with TC that derives from TUB is genetically continuous to the TUB that is detected as intramucosal carcinoma. We have applied CGH and TP53 mutation and LOH analyses to this problem. The CGH profile indicated genetic continuity between POR component and TC and discontinuity between the TC and intramucosal TUB. PORs with TC were characterized by high incidence of wild-type p53 inactivation by mutation and LOH of TP53 or genomic gain of MDM2 that may downregulate p53 not only in POR component but also in TC. The pattern of TP53 mutation was common between the POR components and TC. These findings suggest that wild-type p53 inactivation precedes dedifferentiation of TC to POR. The precursors of POR with TC may thus include early TUBs with this inactivation.