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Human Homologue of a Candidate for the Mom1 Locus, the Secretory Type II Phospholipase A₂ (PLA2S-II), Maps to 1p35-36.1/D1S199¹

Department of Cytogenetics-0130, German Cancer Research Center, Im Neuenheimer Feld 280,D-69120 Heidelberg, Germany [C. P., L. S., M. S., L. C. A.]; Centre d'Etude du Polymorphisme Humain, 27 rue Juliette Dodu, 75010 Paris, France [D. L. P.]; and Department of Microbiology and Immunology, Jefferson Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [L. D. S., A. M. B.]

Mice heterozygous for the dominant Min mutation in their Apc gene develop multiple intestinal neoplasia. Analogously, family members from familial adenomatous polyposis kindreds inheriting mutations in their human 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 found among inbred mouse strains. The secretory type II phospholipase [nonpancreatic Pla2s (type II Pla2s or Pla2s-II)] has been demonstrated to be a candidate for Mom1, and a mutation in Pla2s-II in mice carrying 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 Pla2s-II. We have identified 3 mega-yeast artificial chromosomes that carry PLA2S-II and localized one of them by fluorescence in situ hybridization to the border between 1p35 and 1p36.1. The presence of the microsatellite marker D1S199 in all three clones integrates PLA2S-II into different genetic maps. This highly polymorphic CA repeat D1S199 has previously been shown by us to identify loss of heterozygosity in 48% of sporadic colorectal tumors, indicating that the human homologue of the Pla2s-II/Mom1 locus might be related to human colorectal cancer.

¹ This study was financially supported by Dr. Mildred Scheel Stiftung, Wilhelm Sander-Stiftung, the Deutsche Forschungsgemeinschaft, the Heidelberg-Mannheim Comprehensive Cancer Center, and European Communities Concerted Action "Molecular Cytogenetics of Solid Tumors" Grant BMH1-CT92-0156.

² To whom requests for reprints should be addressed. Phone: 6221-423220; Fax: 6221-423277.

Received 9/26/95. Accepted 10/24/95.

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