Genetic alterations of sporadic colorectal cancer with microsatellite instability, especially characteristics of primary multiple colorectal cancers.
OBJECTIVE
The purpose of this study was to elucidate genetic alterations of sporadic colorectal cancers with Microsatellite instability (MSI).


METHODS
One hundred and ten patients with sporadic colorectal cancer were examined. The MSI was assessed using eight microsatellite markers. In addition, mutation analysis was performed for Transforming growth-beta type II receptor (TGF beta R II), bcl-2 associated X protein (BAX), Insulin-like growth factor II receptor (IGF II R), human MutS homolog 3 (hMSH3), human MutS homolog 6 (hMSH6), human MutS homolog 2 (hMSH2), and human MutL homolog 1 (hMLH1) genes. Tumors with three or more positive loci have been determined to be MSI-H (high-frequency MSI), tumors with one or two positive loci were designated as MSI-L (low-frequency MSI) and tumors lacking apparent instability were designated as MSS (microsatellite stable).


RESULTS
There were 11 cases with MSI-H (MSI-H group) and 99 cases with MSI-L/MSS (MSI-L/MSS group). The frequency of cases with multiple colorectal cancer in the MSI-H group was significantly higher than that of MSI-L and MSS group (81.8% vs. 34.3%, p = 0.0022). The frequency of cases with multiple cancers increased as the number of locus with microsatellite instability increased. Among 11 tumors with MSI-H, 7 indicated mutation of the TGF beta R II (63.6%), whereas no tumor had a mutation of the TGF beta R II among 20 tumors with MSI-L (p = 0.0001). Regarding the BAX, hMSH3, hMSH6 gene, the same trend was obtained as the TGF beta R II gene (18.2% vs. 0%, p = 0.0487, 36.4% vs. 0%, p = 0.0039, 27.3% vs. 0%, p = 0.0140, respectively). Only two cases indicated a somatic point mutation of the hMSH2 gene.


CONCLUSIONS
The multiple occurrence of the colorectal carcinoma may be related to MSI-H as well as the mutation of genes possessing repetitive mononucleotide tracts. Furthermore, we recommend strict follow-up in sporadic colorectal patients that indicate MSI-H.
Abe
Y
Y
Department of Functional Physiology, Nihon University School of Medicine, Tokyo, Japan.
Masuda
H
H
D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm; D005819:Genetic Markers