PURPOSE: A very high frequency of somatic mutations in the transforming growth 
factor-beta signaling component km23 has been reported in a small series of 
ovarian cancers (8 of 19, 42%). Functional studies showed that some mutations 
disrupt km23 function, resulting in aberrant transforming growth factor-beta 
signaling and presumably enhanced tumorigenicity. If verified, this would 
elevate mutation of km23 as the single most frequent somatic event in ovarian 
cancer.
EXPERIMENTAL DESIGN: We sought to verify the frequency of silencing of km23 
among 104 primary ovarian cancers (49 serous, 18 mucinous, 29 endometrioid/clear 
cell, and 8 undifferentiated) as well as 72 breast and 61 colorectal cancers by 
undertaking both somatic mutation and promoter methylation analyses. All four 
exons of km23 were individually amplified from genomic DNA with primers 
complementary to surrounding intronic sequences and analyzed by single-stranded 
conformational polymorphism analysis.
RESULTS: Two germ line polymorphisms were identified, but none of the 237 tumors 
analyzed harbored somatic km23 mutations. In addition, promoter methylation 
analysis showed that in all cases, the 5' CpG island was unmethylated.
CONCLUSIONS: Our data suggest that silencing of km23, either through somatic 
genetic mutation or promoter hypermethylation, is rare in ovarian, breast, and 
colorectal cancers.