Cancer Genetics

This section contains an annotated journal club, updated frequently. The journal club contains links to abstracts of the articles related to genetics, as well as commentary by faculty.

February 2005
Conversion Analysis for Mutation Detection in MLH1 and MSH2 in Patients With Colorectal Cancer, Casey et al. – JAMA, February 16, 2005; Vol 293, No. 7

Commentary:
In this study, the members of the Colon Cancer Family Registry Consortium compare the detection rate for mutations in mismatch repair genes (MLH1, MSH2, and MSH6) between DNA sequencing and conversion analysis. The results confirm that the spectrum of mutations in the mismatch repair genes consists of a high proportion of large genomic deletions and rearrangements, which DNA sequencing does not detect. “Conversion analysis provided an increase of 56% (35/63) in the diagnostic yield of genetic testing compared with genomic DNA sequencing alone.” While these results are encouraging, it is important to consider that the population was selected for patients with histories highly suggestive of HNPCC. Additionally, clinical testing is now available for mismatch repair gene mutations using a combination of DNA sequencing and Southern blot techniques. This study did not address any of the other mutation detection techniques besides DNA sequencing and conversion analysis. Alternate techniques could presumably detect some of the large deletions and rearrangements that were detected by conversion analysis in these samples. Therefore, while this study supports the need for complimentary techniques for the detection of mismatch repair gene mutations, the most efficient and cost effective methodologies have yet to be determined.