3 SECRETORY PHOSPHOLIPASE A(2) GENES THAT MAP TO HUMAN-CHROMOSOME 1P35-36 ARE NOT MUTATED IN INDIVIDUALS WITH ATTENUATED ADENOMATOUS POLYPOSIS-COLI

Mutation of Pla2g2a, a secretory phospholipase A(2) gene, dramatically increases the number of intestinal polyps that develop in the multipl e intestinal neoplasia (Min) mouse, a marine model for adenomatous pol yposis coh in humans. We tested the hypothesis that mutation of the hu man homologue(s) of this gene might be responsible for the more severe phenotype (hundreds of polyps) seen in a subset of individuals with a ttenuated adenomatous polyposis coli (AAPC). DNA sequence analysis dem onstrated that alterations of PLA2G2A, as well as related genes PLA2G2 C and PLA2G5, were evenly distributed between three classes of AAPC su bjects: those with small, intermediate, and large numbers of adenomato us colonic polyps. Among 67 additional unrelated AAPC subjects, a stop mutation In PLA2G2C did not correlate with an increased burden of ade nomatous polyps. Therefore, mutation of the human homologue(s) of muri ne Pla2g2a does not appear to be responsible for phenotypic variation among subjects with AAPC.