A GENE (DLG2) LOCATED AT 17Q12-Q21 ENCODES A NEW HOMOLOG OF THE DROSOPHILA TUMOR-SUPPRESSOR DLG-A

We have isolated a novel cDNA that maps distal to BRCA1 at 17q12-q21, The total sequence predicts a protein of 576 amino acids with three co nserved regions: a 90-amino-acid repeat domain, a SH3 (src homology re gion 3) motif, and a guanylate kinase domain. These conserved regions are shared among members of the discs-large family of proteins that in clude human p55, a membrane protein expressed in erythrocytes, rat PSD -95/SAP90, a synapse protein expressed in brain, Drosophila dig-A, a s eptate junction protein expressed in various epithelia, and human and mouse ZO-1 and canine ZO-2, two tight junction proteins. dig-A has bee n shown to act as a tumor suppressor, and the other members may all be involved in signal transduction through specialized membrane domains with highly organized cytoskeletons and thus are potential tumor suppr essors. Since allelic loss has been reported in the 17q12-q21 region i n breast and ovarian cancer and it appears that BRCA1 is not the targe t of the losses, we looked for somatic alterations in DLG2 in sporadic breast tumors. No evidence for mutation was found, making it unlikely that DLG2 is involved in sporadic breast cancer. (C) 1995 Academic Pr ess, inc.