Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature.
Biochemical evidence of KIT activation, as assessed by KIT phosphorylation and KIT association with phosphatidylinositol (PI) 3-kinase in tumor cell lysates, was largely confined to seminomas with a genomic KIT mutation.
The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10<sup>-13</sup> ) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS).
Among human testicular germ cell tumors (GCTs), seminomas and seminoma components of mixed GCTs have also been shown to express KIT, but only one study has found the c-kit gene mutation at exon 17 in seminoma.
No N-ras mutations were detected in these tumor samples, but two K-ras-2 exon 1 mutations were found in two of the seminoma tumors (stage I and II tumors) using the DGGE technique.
An allelic loss of p53 at exon 4 was detected in five nonseminomas, whereas LOH of p53 at intron 6 occurred in one of the seminoma and two of the nonseminoma samples.
Using the polymerase chain reaction (PCR) and allele specific oligonucleotide hybridization (ASO), mutations were found in five SE (three in NRAS and two in KRAS, all codon 12), and in one NS (KRAS, codon 12).
The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10<sup>-13</sup> ) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS).
No N-ras mutations were detected in these tumor samples, but two K-ras-2 exon 1 mutations were found in two of the seminoma tumors (stage I and II tumors) using the DGGE technique.
To exclude underestimation of the incidence of RAS mutations in TGCTs due to the presence of an excess of wild type alleles in the analyzed sample, a PCR technique preferentially amplifying KRAS alleles with a mutation in codon 12 was applied to all SE.
The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10<sup>-13</sup> ) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS).
EC differentiation to TE and YST entails reprogramming toward the somatic state, with loss of methyl-CpH but de novo methylation of pluripotency loci such as NANOG Extreme methyl-depletion among SE reflects the PGC methylation nadir.
High levels of expression and activating mutations in RAS were mutually exclusive events, and activating mutations in RAS were only identified in the seminoma subtype.Mutations in BRAF were not identified.
We did not identify any tumours with the BRAFV600E mutation and transcriptome analysis revealed no significant differences between hypo- and hyper-methylated seminomas.