Mutations of c-kit gene in bilateral testicular germ cell tumours in Japan

About 10-40% of testicular germ cell tumours (TGCTs) have been reported to have activating c-kit gene mutations. A European study group has reported that most bilateral TGCTs from European patients have c-kit mutations at codon 816, although few unilateral cases harbour the mutations. This implies that the presence of a c-kit mutation in a unilateral TGCT predicts the development of TGCT in the contralateral testis (bilateral disease). However, since little is known about on c-kit gene mutational frequencies in bilateral TGCTs from patients of Asian origin, we examined 12 bilateral TGCTs from seven Japanese patients, along with 39 unilateral TGCTs from Japanese patients, for the presence of c-kit mutations. We analyzed c-kit exons 11 and 17 by PCR followed by direct sequencing, and also analyzed the hotspot mutations at codon 816 by loop-hybrid mobility shift assay, a sensitive PCR-based method. We found c-kit mutations in seven of 39 (18%) unilateral TGCTs: two of the seven mutations were in exon 11 and the others, including four point mutations at codon 816, were in exon 17. No mutations, however, were observed in bilateral TGCTs. Thus, the presence of c-kit gene mutations in TGCTs may not be associated with bilateral diseases, at least in Japan.