THE SECRETORY PHOSPHOLIPASE-A2 GENE IS A CANDIDATE FOR THE MOM1 LOCUS, A MAJOR MODIFIER OF APC(MIN)-INDUCED INTESTINAL NEOPLASIA

Mutations in the APC gene are responsible for various familial and spo radic colorectal cancers. Min mice carry a dominant mutation in the ho molog of the Ape gene and develop multiple adenomas throughout their s mall and large intestine. Quantitative trait loci studies have identif ied a locus, Mom1, which maps to the distal region of chromosome 4, th at dramatically modifies Min-induced tumor number. We report here the identification of a candidate gene for Mom1. The gene for secretory ty pe II phospholipase A2 (Pla2s) maps to the same region that contains M om1 and displays 100% concordance between allele type and tumor suscep tibility. Expression and sequence analysis revealed that Mom1 suscepti ble strains are most likely null for Pla2s activity. Our results indic ate that Pla2s acts as a novel gene that modifies polyp number by alte ring the cellular microenvironment within the intestinal crypt.