HUMAN HOMOLOG OF A CANDIDATE FOR THE MOM1 LOCUS, THE SECRETORY TYPE-II PHOSPHOLIPASE-A2 (PLA2S-II), MAPS TO 1P35-36.1 DIS199/

Mice heterozygous for the dominant Min mutation in their Apc gene deve lop multiple intestinal neoplasia, Analogously, family members from fa milial adenomatous polyposis kindreds inheriting mutations in their hu man APC homologue develop a similar phenotype. Quantitative trait loci studies have identified the Mom1 locus (for modifier of Min-1), which is responsible for part of the genetic variability in polyp number fo und among inbred mouse strains. The secretory type II phospholipase [n onpancreatic Pla2s (type II Pla2s or Pla2s-II)] has been demonstrated to be a candidate for Mom1, and a mutation in Pla2s-II in mice carryin g the Min mutation has been proposed to account for an increased polyp number compared to mice without the Pla2s-II mutation. In this study, we have mapped the chromosomal position of the human homologue of Pla 2s-II. We have identified 3 mega-yeast artificial chromosomes that car ry PLA2S-II and localized one of them by fluorescence in situ hybridiz ation to the border between 1p35 and 1p36.1. The presence of the micro satellite marker D1S199 in all three clones integrates PLA2S-II into d ifferent genetic maps. This highly polymorphic CA repeat D1S199 has pr eviously been shown by us to identify loss of heterozygosity in 48% of sporadic colorectal tumors, indicating that the human homologue of th e Pla2s-III Mom1 locus might be related to human colorectal cancer.