Over-expression of coronin 2a and lack of alterations in transforming growth factor ß receptor I in squamous cell carsinomas of the skin

• Allelic losses in several regions of chromosome 9q have been connected to the development of squamous cell carcinoma (SCC) of the skin. We have studied two candidate genes in the 9q22 region using mutational analysis of genomic DNA as well as immunohistochemistry for assessment of changes in protein expression. The coronin 2A (CORO2A) protein shows strong resemblance to actin-binding proteins, implying a role in cytokinesis or cell motility. It has also been found to be part of the nuclear receptor co-repressor complex involved in transcriptional regulation. We elucidated the exon-intron structure by sequence alignment of the mRNA to a "high-throughput genomic sequence" entry in GenBank. By using single strand conformation analysis and DNA sequencing we found eight silent mutations in tumor DNA, one of which was found in a subset of a normal control population. Surprisingly, immunostaining revealed over-expression in 4/40 tumors. This cannot explain the high frequency of allelic loss in cutaneous secs, but is yet indicating a possible involvement of CORO2A in cutaneous SCC development. The gene for transforming growth factor ß receptor 1 (TßR-I) has previously been positioned to the 9q22 region. TßR-I is part of a protein complex necessary for binding of the TGFß ligand initiating a signaling cascade, which affects downstream targets important for cell cycle regulation. We could not identify any alterations at either protein or DNA level and therefore exclude TßR-I as candidate for cutaneous sec development.

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