Genetic and epigenetic analysis of the putative tumor suppressor km23 in primary ovarian, breast, and colorectal cancers.
OBJECTIVE
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.


METHODS
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.
Campbell
Ian G
IG
Victorian Breast Cancer Research Consortium Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, 8006, Australia. ian.campbell@petermac.org
Phillips
Wayne A
WA
Choong
David Y H
DY
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000517:prevention & control; D056445:Cytoplasmic Dyneins; D017931:DNA Primers; D004398:Dyneins / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000517:prevention & control; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
D017931:DNA Primers; C504797:DYNLRB1 protein, human; D025521:Tumor Suppressor Proteins; D056445:Cytoplasmic Dyneins; D004398:Dyneins