Genomic structure, chromosomal location, and mutation analysis of the human CDC14A gene

Human CDC14A is a dual-specificity phosphatase that shares sequence similar ity with the recently identified tumor suppressor, MMAC1/PTEN/TEP1. By radi ation hybrid mapping, we localized CDC14A to chromosome band 1p21, a region that has been shown to exhibit loss of heterozygosity in highly differenti ated breast carcinoma and malignant mesothelioma. We have mapped the exon-i ntron structure of CDC14A gene and found an in-frame ATG at 14 codons upstr eam of the previously reported start site (GenBank Accession No. AF000367). In screening a panel of 136 cDNAs from tumor cell lines for coding mutatio ns, we have identified a 48-bp in-frame deletion in the cDNA of the breast carcinoma cell line, MDA-MB-436. This deletion is the result of an acceptor splice site mutation (AG to AT) in intron 12 that causes the skipping of e xon 13 in the gene. Loss of expression of the wild-type allele in the same breast cell line supports the possibility that CDC14A may be a tumor suppre ssor gene that is targeted for inactivation during tumorigenesis. (C) 1999 Academic Press.