Abstract
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 131I 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.
Key Points
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Most childhood thyroid cancers are papillary thyroid carcinomas that can present with multiple histological variants; a solid growth pattern of papillary cancer is associated with tumors that develop quickly
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Gene rearrangements predominate in childhood thyroid carcinomas whereas point mutations are rare
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RET/PTC1 and RET/PTC3 are the major rearrangements in childhood papillary thyroid carcinomas; RET/PTC3 correlates with a solid morphology and fast-growing tumors, RET/PTC1 is characteristic of carcinomas with typical papillary architecture
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Head and neck irradiation and internal exposure to radioactive iodine can induce childhood thyroid cancer in a (small) proportion of individuals, and contribute to a life-long increased risk of this disease
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Variations in the latency periods of radiation-induced thyroid cancer indicate the presence of radiation-sensitive or radiation-resistant genotypes, which affect the conditions that lead to disease onset
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Yamashita, S., Saenko, V. Mechanisms of Disease: molecular genetics of childhood thyroid cancers. Nat Rev Endocrinol 3, 422–429 (2007). https://doi.org/10.1038/ncpendmet0499
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DOI: https://doi.org/10.1038/ncpendmet0499
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