Gap junctional intercellular communication is often impaired in
cancers, and the genes which encode the
connexin gap junction proteins are considered to be tumor-suppressor genes. In this study, we analyzed the presence of mutations in the
connexin 37 (Cx37) gene in 22 human hepatic
angiosarcomas, 6 and 4 of which were associated with exposure to
vinyl chloride and
Thorotrast, respectively. The other 12 samples were from patients with no history of exposure to these 2 agents. In 9 samples, a
proline (ACC) to
serine (ACT)
amino acid change in
codon 319 was detected. However,
DNA from non-tumorigenic tissue of the same patients also showed this
amino acid change, suggesting that this is a polymorphism rather than a mutation. Subsequent analysis of 84
DNA samples from normal donors revealed the frequencies of
Pro/Pro,
Pro/Ser and Ser/Ser alleles to be 65.5%, 23.8% and 10.7%, respectively, while among the group of
angiosarcoma patients the corresponding figures were 59.1%, 31.8% and 9. 1%, respectively. Thus, there was no correlation between the polymorphism at
codon 319 and hepatic
angiosarcoma occurrence. However, among the 6 cases of
vinyl chloride-associated
angiosarcoma, the percentages of the polymorphic alleles were 33.3%, 66.7% and 0%, respectively. While the number of samples was too small to allow us to conclude that the Ser319 allele in Cx37 predisposes to this rare type of human
cancer, it may be noted that
codon 319 is located at the cytoplasmic tail of Cx37, where most regulatory sequences reside, and that it could be a site of phosphorylation for some
protein kinases, which may in turn affect the function of Cx37, including intercellular communication.