K-RAS and N-RAS mutations in testicular germ cell tumors

Abstract

Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5 non-seminoma cases (26%) [p = 0.55]. AK-RAS mutation was present in 4 pure seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: One with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.