Screening breast cancer patients for ATM mutations and polymorphisms by using denaturing high-performance liquid chromatography

All 62 coding exons of the ATM gene, along with 10-20 bases of the intronic region flanking each exon, were screened for DNA base sequence alterations by using denaturing high-performance liquid chromatography (DHPLC) in a se ries of 52 breast cancer patients. Six (12%) of these patients exhibited a total of eight different novel germ-line mutations that do not represent co mmon polymorphisms. Of these, three patients possessed four nonconservative missense mutations while two conservative missense and two synonymous muta tions were detected in the other three patients. In addition, 43 patients w ere found to have a total of 141 DNA sequence variations representing 21 di fferent common polymorphisms and rare variants. An analysis of the relation ship between the presence of a novel ATM mutation and either patient demogr aphics or tumor properties demonstrated a significant difference between Af rican Americans (3/ 7 = 43%) and other ethnic groups (3/45 = 7%, P = 0.026) . None of the other characteristics examined was found to be related to mut ation status. (C) 2001 Wiley-Liss, Inc.