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Vol. 22, No. 6, 2001
Issue release date: November–December 2001 (December 2001)
Tumor Biol 2001;22:348–366

The CA 125 Gene: An Extracellular Superstructure Dominated by Repeat Sequences

O’Brien T.J. · Beard J.B. · Underwood L.J. · Dennis R.A. · Santin A.D. · York L.
aDepartment of Obstetrics and Gynecology and bDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Ark., USA

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CA 125 has long presented problems to both clinicians and investigators because there was no definitive information on its structure and function. Here, we describe our work on cloning the CA 125 gene with the anticipation that such information will provide the basis for understanding its structure and its physiologic role in both normal and malignant tissues. The CA 125 protein core is composed of a short cytoplasmic tail, a transmembrane domain and an extraordinarily large glycosylated extracellular structure. This structure is dominated by a repeat domain composed of 156 amino acid repeat units which encompass the epitope binding sites. The molecule also includes an amino terminal domain of serine/threonine-rich sequences which would account for most of the O-glycosylation known to be present in CA 125. CA 125 is an unusually large transmembrane glycoprotein. Its release from the surface of the cell is most probably dependent on cytoplasmic phosphorylation followed by proteolytic cleavage. The extracellular domain is characterized by a large number of repeat units (probably 60+) which encompass an interactive disulfide bridged cysteine-loop and the site of OC125 and M11 binding. Sequencing the gene provides us with the ability to initiate the quest to understand the biological function of CA 125.

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