RESUMO
In order to compare the frequency of damage to the transforming growth factor TGF-beta receptor type II gene (RII gene) and microsatellite instability (MIN) in oncogenesis of sporadic and hereditary cancer of gastrointestinal tract (GIT), 4 groups of carcinomas were analyzed. They included sporadic gastric (GC), family gastric (FGC), sporadic colorectal (CC) and hereditary nonpolyposis colorectal (HNPCC) carcinomas having appropriate clinical and pathological characteristics. Each group consisted of two types of carcinomas, one of them showing MIN. The RII gene damage occurred in 89% of GC (8 cases out of 9), 86% of CC (6 out of 7), 71% of FGC (5 out of 7), 50% of HNPCC (3 out of 6) for carcinomas coupled with MIN, whereas only in 6% (1 out of 18) of GC and 5% (1 out of 22) of CC for carcinomas without MIN. No damage to RII gene was found in the cases of hereditary carcinomas which did not show MIN though the number of cases analyzed was not sufficient for final conclusions (3 cases of FGC and 3 HNPCC). The data revealed a correlation between the MIN phenotype and mutations in RII gene both for sporadic (p < 0.001) and for hereditary (p < 0.02) cases. For all 4 groups the frequency of RII gene damage was found for early and advanced carcinomas. This suggests that the deficiency of TGF-beta receptor complex in both sporadic and hereditary carcinomas of GIT is revealed at early stages of tumor development and consequently may be responsible for tumor progression. The correlation between RII gene damages and MIN in GIT carcinoma cells suggests that genetic change predetermined the neoplasia of colorectal and gastric epithelium and partially overlapped for both sporadic and hereditary cases.
Assuntos
Dano ao DNA/genética , DNA de Neoplasias/genética , Neoplasias Gastrointestinais/genética , Repetições de Microssatélites/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Progressão da Doença , Neoplasias Gastrointestinais/metabolismo , Humanos , Mutação , Fenótipo , Neoplasias Gástricas/genéticaRESUMO
Microsatellite instability (MIN) of human genome, i.e. instability of very short (1-5 nt) DNA tandem repeats, points to a deficiency in the mismatch repair system (MMR). To investigate the role of MMR in sporadic and hereditary carcinogenesis in the gastrointestinal tract, four types of carcinomas were compared: sporadic (GC), familial (FGC) gastric carcinoma, sporadic colorectal (CC) and hereditary nonpolyposis colorectal (HNPCC) carcinoma. No significant difference in MIN frequency was found between GC (9 out of 27) (33%) and CC (7 out of 29) (24%). In hereditary carcinoma group, MIN occurrence appeared 2-3 times as high: FGC in 7 out of 10 (70%) and HNPCC in 6 out of 8 patients (75%). No significant differences were recorded in MIN occurrence at early and later stages of the disease in all groups. Therefore, it can be suggested that disorders in the MMR develop at earlier stages of carcinogenesis and may be responsible for tumor progression.
