Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in Japan.
Most tumors of patients with Lynch syndrome and a fraction of sporadic colorectal cancers (CRCs) exhibit high levels of microsatellite instability (MSI) at mono- and dinucleotide repeat loci. A different type of instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been found in non-colonic cancers. Our previous study demonstrated that EMAST is common in sporadic CRC. Here, we focused on the relationships between EMAST and other genomic instability parameters or clinicopathological features in an unselected series of 88 sporadic CRCs. Of the tumors in the sample, 4 (4.5%) were MSI-high (MSI-H), 9 (10.2%) were MSI-low (MSI-L) and 75 (85.2%) were microsatellite stable. EMAST status was determined using 7 EMAST markers. Fifty-three (60.2%) tumors without MSI-H showed instability at >or=1 EMAST loci. All 4 MSI-H tumors showed instability at several EMAST loci. Instability profiles of MSI-H tumors at EMAST loci were more complex than those of non-MSI-H tumors. A tendency of positive association was observed between MSI-L and EMAST (P=0.023). The frequency of loss of heterozygosity (LOH) for the 14 loci in EMAST-positive tumors was significantly higher than negative tumors (P=0.048). Among the clinicopathological parameters, only tumor location at the distal colon was associated with EMAST-negative tumors (P=0.0084, one-tailed). A relatively higher frequency of well-differentiated adenocarcinomas was observed in EMAST tumors as opposed to non-EMAST tumors, though the survival rate was similar. These results suggest that overlapping mechanisms that cause MSI-L, EMAST and LOH in CRCs may exist.
Yamada
Kanae
K
Department of Molecular Biology, Toho University Faculty of Medicine, Tokyo, Japan.
Kanazawa
Shinsaku
S
Koike
Junichi
J
Sugiyama
Hisahiko
H
Xu
Can
C
Funahashi
Kimihiko
K
Boland
C Richard
CR
Koi
Minoru
M
Hemmi
Hiromichi
H
D000230:Adenocarcinoma / Q000235:genetics*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007564:Japan; D019656:Loss of Heterozygosity; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics* / Q000502:physiology