Abstract
Gain‐of‐function mutations of the c‐kit gene and the expression of phosphorylated KIT are found in most gastrointestinal stromal tumors and mastocytosis. Further, almost all gonadal seminomas/ dysgerminomas exhibit KIT membranous staining, and several reports have clarified that some (10–25%) have a c‐kit gene mutation. But, whether intracranial germinomas also have a c‐kit gene mutation remains unsolved. To elucidate the presence, frequency, and location of c‐kit gene mutations in intracranial germinomas, we analyzed five mutational hot spots (exons 9, 10, 11, 13, and 17) in the c‐kit genomic DNA of 16 germinomas using polymerase chain reaction and direct sequencing. We found c‐kit gene mutations at exon 11 (W557C) or 17 (D816V, D820V, and N822Y) in four germinomas (25.0%), although no statistically significant difference in any clinicopathological factor was found between patients with or without mutations. These results are similar to those seen in gonadal seminoma/dysgerminoma patients, and confirm that intracranial germinomas are exact counterparts of gonadal seminomas/dysgerminomas, as would be expected on histological and immunohistochemical grounds. Moreover, molecular targeting drugs such as imatinib mesylate (STI571), which is a selective inhibitor of KIT, might be promising agents for the treatment of intracranial germinomas with c‐kit gene mutations.
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