Version of Record online: 26 APR 2004
Copyright © 2004 American Cancer Society
Volume 100, Issue 11, page 2486, 1 June 2004
How to Cite
Geisler, J. P. and Buller, R. E. (2004), Author reply. Cancer, 100: 2486. doi: 10.1002/cncr.20249
- Issue online: 18 MAY 2004
- Version of Record online: 26 APR 2004
Thank you for the chance to respond to the comments made by Pal et al. A number of interesting queries were raised in their letter. We will attempt to answer each one individually.
First, we were not attempting to estimate the frequency of mismatch repair (MMR) gene mutations in the study population. We concur that missense mutations are missed by our methods. The goal of the article was to determine whether high microsatellite instability (MSI) could be explained by epigenetic silencing and/or truncating mutations.
Second, normal control tissue for MSI testing was taken from peripheral blood DNA. Normal ovarian tissue used for methylation-specific polymerase chain reaction was taken from patients without malignancy so that no contamination of the normal control tissue would be possible.
Next, we agree that the proportion of ovarian carcinomas attributable to hereditary nonpolyposis colorectal carcinoma (HNPCC) is not yet known. Furthermore, Watson et al. reported that 84% of ovarian carcinomas that were associated with HNPCC were early stage.1 We again did not attempt to determine a population frequency. In our study, patients were chosen based solely on the availability of consecutive snap-frozen specimens. As we and other authors have previously shown, other familial cancer syndromes such as those involving BRCA1 and BRCA2 also involve peritoneal and fallopian tube carcinomas.2 In fact, based on this limited sample, fallopian tube carcinomas may play a role in HNPCC.3
Further analysis of the high-frequency MSI tumors, including direct sequencing of MMRs, has been undertaken and will be reported at a later date.