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.
However, protein expression of OCT3/4 and AP2y was weak and these JKT-1 cells expressed SOX2, a marker of embryonal carcinoma and did not express c-KIT usually expressed in most seminoma.
This study shows that expression of p53, Ki67, and CD30 and loss of CD117 expression fail to predict the presence of clinical metastasis at diagnosis of testicular seminoma and do not correlate with other histopathological risk factors in clinical stage I patients.
The c-kit gene encodes a tyrosine kinase receptor (KIT) that is required in normal spermatogenesis and is expressed in seminomas and dysgerminomas, a subset of human germ cell tumors (GCTs).
The data obtained in both groups did not differ in any of the investigated biologic markers. c-KIT was detected in the one case of pure seminoma studied and in the seminomatous components of combined tumors.
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.
Taken together with activating mutations of KIT in exon 17 identified in 13% of seminomas, this suggests that the KIT gene product plays a role in the progression of CIS towards seminoma, the further understanding of which may lead to novel less toxic therapeutic approaches.
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.
Overexpression of KIT, a tyrosine kinase receptor protein encoded by the proto-oncogene c-kit, is observed in human neoplasms such as gastrointestinal stromal tumors (GISTs), myeloproliferative disorders, melanoma and 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.
Based on genome-wide expression profiling, SOX17 was found to be present, instead ofSOX2, in early germ cells and their malignant counterparts, CIS and seminoma.
So, SOX2 is an essential factor in acquiring an EC-like cell fate from seminomas.A small population of differentiated cells was identified resembling a mixed non-seminoma.
Embryonic stem cell regulator SOX2 and downstream targets of the Nodal pathway were up-regulated in embryonal carcinoma only but not in IGCNU/seminoma.
Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma.
Strikingly, these compounds inhibited the proliferation of pluripotent cancer cells including teratocarcinoma, embryonic carcinoma, and seminoma or embryonic stem cells that express the stem cell markers Oct4 and Sox2 while displaying minimum growth-inhibitory effects on non-pluripotent cancer or normal somatic cells.