Ohtani H, Yashiro M, Onoda N, Nishioka N, Kato Y, Yamamoto S, Fukushima S, Hirakawa-Ys Chung K
First Department of Surgery, Osaka City University Medical School, Osaka, Japan.
Int J Cancer. 2000 Jun 1;86(5):678-83. doi: 10.1002/(sici)1097-0215(20000601)86:5<678::aid-ijc12>3.0.co;2-o.
Colorectal (CRC) and gastric cancers (GC), the most common gastrointestinal malignancies, have been known to develop occasionally in a same patient. Previous studies have focused on the etiology of patients with multiple primary gastric and colorectal cancer (MPGCC); however, the carcinogenic process of MPGCC remains unclear. In this study, we have examined the genetic alterations in MPGCC in order to clarify the carcinogenic pathway. Twenty patients with sporadic MPGCC were examined for microsatellite instability (MSI) and frameshift mutations of target genes such as TGFbetaRII, BAX and IGFIIR. In 10 (50%) of 20 patients with MPGCC, MSI was present at least at 1 lesion of GC or CRC. Four (50%) of 8 cases with synchronous MPGCC displayed MSI in both GC and CRC, while only 1 (8%) of 12 cases of metachronous MPGCC exhibited MSI in both organs. Carcinogenic process of MPGCC was fairly associated with the MSI pathway, particularly in cases of synchronous MPGCC. MSI was found in 5 (25%) of 20 GCs and in 10 (50%) of 20 CRCs. MSI was involved more closely in CRC than in GC among MPGCC. Although most frameshift mutations at target genes were found in the MSI-positive MPGCC, infrequent mutations were observed in the genes. Frameshift mutation was found in only 1 of 5 cases of MSI-positive GC at TGFbetaRII. Only 2 of 10 cases of CRC with MSI showed mutation at TGFbetaRII, and 1 case also showed mutation at BAX and IGFIIR. Our findings suggest that TGFbetaRII, BAX and IGFIIR are not the main target genes for carcinogenesis in MSI-positive MPGCC.
结直肠癌（CRC）和胃癌（GC）是最常见的胃肠道恶性肿瘤，已知偶尔会在同一患者中发生。先前的研究主要集中在多原发性胃癌和结直肠癌（MPGCC）患者的病因上；然而，MPGCC的致癌过程仍不清楚。在本研究中，我们检测了MPGCC中的基因改变，以阐明致癌途径。对20例散发性MPGCC患者进行了微卫星不稳定性（MSI）及TGFbetaRII、BAX和IGFIIR等靶基因的移码突变检测。在20例MPGCC患者中的10例（50%）中，MSI至少在GC或CRC的1个病灶中存在。8例同时性MPGCC患者中有4例（50%）在GC和CRC中均显示MSI，而12例异时性MPGCC患者中只有1例（8%）在两个器官中均表现出MSI。MPGCC的致癌过程与MSI途径密切相关，尤其是在同时性MPGCC病例中。在20例GC中有5例（25%）发现MSI，在20例CRC中有10例（50%）发现MSI。在MPGCC中，MSI与CRC的关系比与GC更为密切。虽然大多数靶基因的移码突变在MSI阳性的MPGCC中被发现，但在这些基因中观察到的突变并不常见。在5例MSI阳性的GC中，仅1例在TGFbetaRII基因发现移码突变。10例MSI阳性的CRC中，只有2例在TGFbetaRII基因发生突变，1例在BAX和IGFIIR基因也发生突变。我们的研究结果表明，TGFbetaRII、BAX和IGFIIR不是MSI阳性MPGCC致癌的主要靶基因。
