Mutations of BRAF and RAS are rare events in germ cell tumours

International Journal of Cancer. Journal International Du Cancer
Florian SommererAndrea Tannapfel

Abstract

The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals. Recently, somatic missense mutations in the BRAF gene have been detected in a variety of human tumors. We have studied male germ cell tumours (GCT) for probable mutations of the BRAF and Ras oncogene. Microsatellite instability (MSI) was analysed using mono- or di-nucleotide marker. Mutational analysis of 62 GCT (30 seminomas and 32 nonseminomas) was performed after microdissection of the different tumour components. The expression of Erk1/2, an important downstream point of convergence in the Ras-RAF-MEK-Erk pathway was assessed immunohistochemically. Activating BRAF missense mutations were identified in 3 out of 32 cases of nonseminomas (9%) but not in seminomas. The mutations were 1796T>A mutations and were found within the embryonic carcinoma component of these tumors. Two out of 30 seminomas (7%) and 3 out of 32 nonseminomas (9%) exhibited KRAS gene mutations. MSI was observed in 4 out 62 tumours (7%) [1 seminoma and 3 nonseminomas (embryonal carcinoma)]. All of the microsatellite instable embryonal carcinomas had a mutated BRAF gene. All 5 GCT with RAS mutations had a...Continue Reading

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