Mechanisms of Disease: molecular genetics of childhood thyroid cancers

Childhood thyroid cancers are uncommon and have a fairly good prognosis. Papillary adenocarcinoma is the most prevalent malignant tumor of the thyroid in children and adults with radiation-induced or sporadic cancer. The incidence of thyroid cancer in children increased dramatically in the territories affected by the Chernobyl nuclear accident; this increase is probably attributable to I-131 and other short-lived isotopes of iodine released into the environment. There was a broad range of latency periods in children who developed thyroid cancer; some periods were less than 5 years. The mutational spectrum of childhood thyroid cancers demonstrates that gene rearrangements that lead to the activation of mitogen-activated protein kinase signaling seem to have a pivotal role; point mutations are rare. So far none of the cancer genes or tumor suppressors, or a peculiar gene expression pattern, has been specifically implicated in radiation-induced thyroid carcinogenesis. The frequency of certain oncogenes does, however, vary in tumors that develop after different periods of latency. Such differences in the distribution of gene abnormalities in radiation-related cancers implies that they associate with patients' age at exposure and diagnosis, clinicopathological manifestations of disease and depend on an individual's genetic characteristics. Here we review results of pathological and molecular studies in childhood thyroid cancer.