TTC4, a novel candidate tumor suppressor gene at 1p31 is often mutated in malignant melanoma of the skin

A novel candidate tumor suppressor gene, TTC4, on chromosome 1p31 has been described recently. Since aberrations in this region have been detected in malignant melanoma, we investigated DNA of paraffin-embedded sections from 16 typical naevi, 19 atypical naevi, 32 primary melanomas (15 superficial s preading melanomas, 17 nodular melanomas) and 25 metastases and DNA from fo ur melanoma cell lines by PCR and direct sequencing analysis for mutations in all exons of TTC4. Tumors comprised a wide range of thickness (Breslow i ndex) and Clark levels. No mutations could be detected in typical or atypic al naevi, but we found se, cn different point mutations in the tumor sample s, sis of them causing an amino acid change. Ten melanoma samples belonging to nine patients showed one or more of these mutations. In detail, in sis of 25 metastases, in two of 17 nodular melanomas and in two of 15 superfici al spreading melanomas point mutations could be detected, In two cell lines , a loss of a whole exon could be demonstrated and in one cell line we foun d a point mutation. In addition, three polymorphisms were found. Our findin gs indicate that TTC4 may participate in the pathogenesis of malignant mela nomas of the skin.