Genomic structure, chromosomal location, and mutation analysis of the human CDC14A gene.
Human CDC14A is a dual-specificity phosphatase that shares sequence similarity with the recently identified tumor suppressor, MMAC1/PTEN/TEP1. By radiation hybrid mapping, we localized CDC14A to chromosome band 1p21, a region that has been shown to exhibit loss of heterozygosity in highly differentiated breast carcinoma and malignant mesothelioma. We have mapped the exon-intron structure of CDC14A gene and found an in-frame ATG at 14 codons upstream of the previously reported start site (GenBank Accession No. AF000367). In screening a panel of 136 cDNAs from tumor cell lines for coding mutations, 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 exon 13 in the gene. Loss of expression of the wildtype allele in the same breast cell line supports the possibility that CDC14A may be a tumor suppressor gene that is targeted for inactivation during tumorigenesis.
Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, Utah, 84108, USA. akcw1@yahoo.com
A K
AK
Wong
Y
Y
Chen
L
L
Lian
P C
PC
Ha
K
K
Petersen
K
K
Laity
A
A
Carillo
M
M
Emerson
K
K
Heichman
J
J
Gupte
S V
SV
Tavtigian
D H
DH
Teng
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D006224:Cricetinae; D004252:DNA Mutational Analysis; D005796:Genes / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases; D014407:Tumor Cells, Cultured
D010744:Phosphoric Monoester Hydrolases; C120902:CDC14A protein, human; D017027:Protein Tyrosine Phosphatases