ABSTRACT
BACKGROUND: Genetic instability is known as a cause of oncogenesis. Though Rad18 is reported to function in a post replication mismatch repair system, the relation between the status of Rad18 and human tumorigenesis has not been described so far. METHODS: Mutation analysis of 34 human cancer cell lines and 32 non small cell lung cancer (NSCLC) tissues were performed by RT-PCR SSCP. Expression level of Rad18 was measured by real time RT-PCR. Stable transfectant was constructed for in vitro study. RESULTS: No mutation was found in both cancer cell lines and NSCLC tissues. A single nucleotide polymorphism (SNP) at codon 302 was detected in 51.5% of the cell lines and 62.5% of NSCLC tissues. Interestingly, Rad18 was homozygously deleted in a pulmonary adenocarcinoma cell line PC3. Furthermore, there was no difference in the expression level of wild type Rad18 and Rad18 with SNP. The growth, cell morphology, sensitivity to anti-cancer drugs and in vitro DNA repair activity between wild type Rad18 and Rad18 with SNP revealed to have no difference in vitro. CONCLUSION: Though the frequency of SNP was tended to be higher in NSCLC patients than healthy volunteers (57.7%), as the difference was not significant, we have concluded that there is no relation between Rad18 SNP and lung cancer development.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Lung Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Neoplasms/genetics , Neoplasms/pathology , Polymorphism, Single-Stranded Conformational , Reverse Transcriptase Polymerase Chain Reaction , Ubiquitin-Protein LigasesABSTRACT
A 53-year-old Japanese woman with bilateral ovarian tumors consulted our department. Gastroendoscopy disclosed 16 superficial depressed gastric lesions, and the histopathological diagnosis of the biopsy specimens was poorly differentiated adenocarcinoma and signet-ring cell carcinoma. Computed tomography (CT), ultrasonography (US), and positron emission tomography (PET) examinations revealed no other metastasis except for that observed in the ovaries. We performed a total gastrectomy with radical lymph node dissection and bilateral ovarian resection. A postoperative histological examination revealed 43 isolated gastric lesions which were scattered over the entire resected stomach; they were all confined to the mucosa. Cancer cell invasion in the lymphatics was detected only in the submucosal region beneath the main tumor. Both ovarian tumors were diagnosed as metastasis of signet-ring cell carcinoma (Krukenberg tumor). Adjuvant chemotherapy with irinotecan (CPT-11) and low-dose cisplatin (CDDP) was given on an outpatient basis, but 1 year after the surgery, carcinomatous pericarditis occurred. Administration of mitomycin C (MMC) into the pericardial space was performed twice; however, unfortunately, the patient died 13 months after surgery.
