in detecting a small fraction of mutated alleles in the presence of a high excess normal alleles, which is frequently the case with clinical cancer samples (16) . As a less expensive alternative, rapid pre-screening methods such as SSCP, DGGE, dHPLC, CCM, CDCE or HR-melting are widely utilized to identify DNA fragments that contain mutations prior to performing full sequencing (14, (16) (17) (18) (19) (20) . Enzymatic mutation detection based on mismatch scanning enzymes like MutY, TDG or T4 endonuclease VII for mutation pre-screening has also been employed (21) (22) (23) (24) (25) , albeit with modest success since these enzymes cannot detect all possible mutations and deletions (22) and some of them have substantial activity on homoduplex DNA (16) . Recently an enzymatic mutation scanning method based on the Surveyor TM (CELI/II) nuclease (26, 27) combined with dHPLC or gel electrophoresis detection was introduced that shows satisfactory selectivity and reliability (1% mutant to wild-type alleles is detectable) while it also identifies all base substitutions and small deletions that are important to cancer (17, 28) or to biotechnology and plant genetic applications [TILLING method (29) (30) (31) (32) (33) (34) ]. While reliable, the use of dHPLC for examining Surveyor TM -generated DNA fragments is a slow endpoint detection method restricted to examining a single DNA fragment at a time and the resulting DNA fragments cannot be sequenced. This limits analysis of cancer specimens when numerous samples or genetic regions need to be screened.