BCL10 single nucleotide polymorphism and its association with CSF dissemination of primary intracranial germ cell tumors.
BACKGROUND
Intracranial germ cell tumors (GCTs) are rare neoplasms. Little is known about the pathogenesis of these tumors. The BCL10 gene, a proapoptotic signaling molecule involved in the Apaf-1/caspase-9 cell death pathway, may act as a tumor suppressor gene in multiple types of tumors including testicular GCTs.


METHODS
To evaluate whether alterations in the BCL10 gene play a role in the genesis of intracranial GCTs, we analyzed the BCL10 gene in 10 pure germinomas (PGs) and 10 nongerminomatous GCTs.


RESULTS
We found no inactivating mutations; however, 5 of 10 PGs and 1 of 10 nongerminomatous GCTs manifested specific single nucleotide polymorphisms (SNPs) that carried an amino acid substitution at codon 5 in exon 1 or codon 162 in exon 3. This SNP occurs at higher frequency in patients with PGs than healthy individuals (p = 0.07). CSF dissemination occurred in 4 of our 6 patients manifesting SNP (p = 0.037).


CONCLUSIONS
Our data suggest that this specific SNP in the BCL10 gene may be partly responsible for the tumorigenesis of PG in Japanese individuals, and may be associated with the aggressive nature of these tumors.
Hayashi
Yutaka
Y
Department of Neurosurgery, Kanazawa University Hospital, Kanazawa, Japan. yuh@ns.m.kanazawa-u.ac.jp
Watanabe
Takuya
T
Nakada
Mitsutoshi
M
Kita
Daisuke
D
Hayashi
Yasuhiko
Y
Uchiyama
Naoyuki
N
Hamada
Jun-ichiro
J
D048868:Adaptor Proteins, Signal Transducing / Q000134:cerebrospinal fluid* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D018237:Germinoma / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human