The Human Plakoglobin Gene Localizes on Chromosome 17q21 and is Subjected to Loss of Heterozygosity in Breast and Ovarian Cancers

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-07, Vol.92 (14), p.6384-6388
• Main Authors: Aberle, H, Bierkamp, C, Torchard, D, Serova, O, Wagner, T, Natt, E, Wirsching, J, Heidkämper, C, Montagna, M, Lynch, H T
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Sequence; Animals; Arginine; Base Sequence; Blotting, Southern; BRCA1 Protein; Breast cancer; breast carcinoma; Breast Neoplasms - genetics; Cell Adhesion Molecules - genetics; Cell Line; chromosome 17; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 17; Complementary DNA; Cosmids; Cricetinae; Cytoskeletal Proteins - genetics; D17S858 locus; Desmoplakins; DNA; DNA - analysis; DNA - genetics; DNA Primers; DNA, Neoplasm - analysis; DNA, Neoplasm - genetics; Exons; Family; Female; gamma Catenin; Genes; Genetic Markers; Genetic mutation; Genetics; Histidine; Human genetics; Humans; Hybrid Cells; KRT10 gene; loss of heterozygosity; man; Mice; Molecular Sequence Data; Neoplasm Proteins - genetics; Ovarian cancer; Ovarian Neoplasms - genetics; ovaries; plakoglobin; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Transcription Factors - genetics; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.14.6384

The gene encoding human plakoglobin was mapped to chromosome 17q12-q22. An intragenic restriction fragment length polymorphism was used to localize the plakoglobin gene distal to locus KRT10 and proximal to the marker D17S858. The plakoglobin gene colocalizes with the polymorphic 17q21 marker UM8 on the same cosmid insert. This subregion of chromosome 17 is known to be particularly subjected to genetic alterations in sporadic breast and ovarian tumors. We show loss of heterozygosity of the plakoglobin gene in breast and ovarian tumors. We have identified a low-frequency polymorphism in the plakoglobin coding sequence which results in an arginine to histidine substitution at amino acid position 142 of the protein, as well as a silent mutation at nucleotide position 332 of the coding sequence. This polymorphism allowed us to demonstrate an allelic association of plakoglobin with predisposition to familial breast and ovarian cancers. Our results, together with the present knowledge about the biological function of plakoglobin, suggest that plakoglobin might represent a putative tumor suppressor gene for breast and ovarian cancers.