Sequencing is often considered the gold standard for comprehensive mutation analysis. Multi-capillary electrophoresis, re-sequencing arrays or pyrosequencing provide platforms for highly parallel genetic analysis (7) (8) (9) (10) (11) (12) (13) . However, the expense associated with these techniques is currently high both for instrumentation and for runningcosts. Since somatic mutations for most genes are relatively rare events it can be inefficient to scan for mutations using expensive approaches that in several cases provide unnecessary data (14, 15) . Another issue with direct sequencing or re-sequencing arrays is the difficulty *To whom correspondence should be addressed. Tel: +1-617-525-7122; Fax: +1-617-587-6037; Email: mmakrigiorgos@partners.org ß 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.