A gene (DLG2) located at 17q12-q21 encodes a new homologue of the Drosophila tumor suppressor dIg-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 conserved regions: a 90-amino-acid repeat domain, a SH3 (src homology region 3) motif, and a guanylate kinase domain. These conserved regions are shared among members of the discs-large family of proteins that include human p55, a membrane protein expressed in erythrocytes, rat PSD-95/SAP90, a synapse protein expressed in brain, Drosophila dIg-A, a septate junction protein expressed in various epithelia, and human and mouse ZO-1 and canine ZO-2, two tight junction proteins. dIg-A has been 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 suppressors. Since allelic loss has been reported in the 17q12-q21 region in breast and ovarian cancer and it appears that BRCA1 is not the target 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.
Mazoyer
S
S
CRC Human Cancer Genetics Research Group, Addenbrooke's Hospital, Cambridge, United Kingdom.
Gayther
S A
SA
Nagai
M A
MA
Smith
S A
SA
Dunning
A
A
van Rensburg
E J
EJ
Albertsen
H
H
White
R
R
Ponder
B A
BA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D004285:Dogs; D004330:Drosophila; D029721:Drosophila Proteins; D005260:Female; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor; D016678:Genome; D006801:Humans; D007301:Insect Hormones / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D051381:Rats; D016415:Sequence Alignment; D017421:Sequence Analysis; D025521:Tumor Suppressor Proteins
D029721:Drosophila Proteins; D007301:Insect Hormones; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila