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Genes, chromosomes and the development of testicular germ cell tumors of adolescents and adults
Author(s) -
McIntyre Alan,
Gilbert Duncan,
Goddard Neil,
Looijenga Leendart,
Shipley Janet
Publication year - 2008
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20562
Subject(s) - gonocyte , biology , kras , cancer research , germ cell tumors , embryonal carcinoma , embryonic stem cell , microrna , oncogene , germ cell , germ layer , stem cell , cellular differentiation , genetics , pathology , gene , cell cycle , mutation , medicine , chemotherapy , induced pluripotent stem cell
Testicular germ cell tumors (TGCTs) of adults and adolescents are thought to be derived from primordial germ cells or gonocytes. TGCTs develop postpuberty from precursor lesions known as intratubular germ cell neoplasia undifferentiated. The tumors can be divided into two groups based on their histology and clinical behavior; seminomas resemble primordial germ cells or gonocytes and nonseminomas resemble embryonic or extraembryonic tissues at various stages of differentiation. The most undifferentiated form of nonseminoma, embryonal carcinoma, resembles embryonic stem cells in terms of morphology and expression profiling, both mRNAs and microRNAs. Evidence supports both environmental factors and genetic predisposition underlying the development of TGCTs. Various models of development have been proposed and are discussed. In TGCTs, gain of material from the short arm of chromosome 12 is invariable: genes from this region include the proto‐oncogene KRAS , which has activating mutations in ∼10% of tumors or is frequently overexpressed. A number of different approaches to increase the understanding of the development and progression of TGCTs have highlighted the involvement of KIT, RAS/RAF/MAPK, STAT, and PI3K/AKT signaling. We review the role of these signaling pathways in this process and the potential influence of environmental factors in the development of TGCTs. © 2008 Wiley‐Liss, Inc.