This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Campbell, I. G. Articles by Choong, D. Y.H. Search for Related Content PubMed PubMed Citation Articles by Campbell, I. G. Articles by Choong, D. Y.H.

Genetic and Epigenetic Analysis of the Putative Tumor Suppressor km23 in Primary Ovarian, Breast, and Colorectal Cancers

Authors' Affiliations: ¹ Victorian Breast Cancer Research Consortium Cancer Genetics Laboratory and ² Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre; and Departments of ³ Pathology and ⁴ Surgery (St Vincent's Hospital) University of Melbourne, Melbourne, Victoria, Australia

Requests for reprints: Ian G. Campbell, Victorian Breast Cancer Research Consortium Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Level 2, Locked Bag No. 1. A'Beckett Street, Melbourne, 8006, Australia. Phone: 61-3-96561803; Fax: 61-3-96561411; E-mail: ian.campbell{at}petermac.org.

Purpose: A very high frequency of somatic mutations in the transforming growth factor-ß 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-ß 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.