Pediatric Cancers

Abstract

While cancers in children and adolescents are overall rare, some cancer types occur predominantly in children and adolescents. Typical pediatric cancers share characteristics like few genetic alterations and disturbed cell differentiation, and occur more often in children with inherited syndromes. Retinoblastoma exemplifies these characteristics. Almost all cases are caused by biallelic RB1 inactivation, followed by variable “third event” mutations. Wilms tumors are genetically more heterogeneous. These nephroblastomas arise from regions of the develo** kidney that have failed to complete differentiation. Some Wilms tumors are caused by germline or somatic mutations in WT1, but the disease can also be caused by mutations in genes encoding other transcription factors, chromatin regulators, and miRNA-processing proteins required for nephrogenesis. The WT1 transcription factor is involved in the development and differentiation of the genitourinary tract. Wilms tumors contain moreover epigenetic alterations in the chromosome 11p15.5 imprinted region. Testicular germ cell tumors (TGCT) typically manifest in young men. They are classified into seminomas and non-seminomas. Seminoma cells resemble primordial germ cells whereas the characteristic cells of non-seminomas, embryonal carcinoma cells, rather resemble embryonic stem cells and may further differentiate into various embryonic, extra-embryonic, and somatic cell types. Almost all TGCT can now be successfully treated by surgery and chemotherapy. TCGT appear to be caused predominantly by copy number changes, affecting especially chromosome 12p and by epigenetic alterations. In seminomas, point mutations in the KIT tyrosine kinase contribute. DNA methylation and miRNA expression patterns in TCGT are distinctive and can be exploited for diagnostics.