Abstract
BACKGROUNDGain of short arm of chromosome 12 (12p) is commonly observed in testicular germ cell tumors (tGCTs). 12p gain is also frequently seen in intracranial GCTs (iGCTs). However, little is known about the clinical significance of 12p gain in iGCTs.MATERIALS AND METHODSWe have collected over 200 fresh frozen tissue samples of iGCTs through the Intracranial Germ Cell Tumor Genome Analysis Consortium in Japan. Firstly, we analyzed DNA methylation status in 83 iGCTs, 3 seminomas and 6 normal control samples using Infinium Human Methylation 450K BeadChip array (Illumina, CA). Idat files were processed using R (Version 3.5.3) and minfi package (1.30.0) to generate copy number variations. Compared with average genome-wide copy number level, 12p gain was determined. Then, 58 iGCTs with clinicopathological information were analyzed for progression-free survival (PFS) and overall survival (OS). Those tumors that consist of only either germinoma and/or mature teratoma components were classified as Favorable Histology (FH) and all the others that contains malignant histological components were classified as Unfavorable Histology (UFH).RESULT12p gain was observed in 100% (3/3) of seminoma, 13.6% (3/22) of germinoma, 16.7% (1/6) of mature teratoma, 25% (1/4) of immature teratoma, 55% (11/20) of mixed germ cell tumor, 100% (4/4) of yolk sac tumor, 100% (1/1) of embryonal carcinoma, and 100% (1/1) of choriocarcinoma. In total, 44.6% (37/83) of iGCT showed 12p gain. Regarding histological classification, the 12p gain rate in UFH (72%, 18/25) was significantly higher than that in FH (12.1%, 4/33, P<0.01). Both PFS and OS were significantly worse in iGCTs with 12p gain (PFS: P=0.027, OS: P=0.0012). DISCUSSION12p gain can be a molecular marker to predict prognosis and histological malignancy in iGCTs.
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