Pediatric oncology
Section snippets
Scope of childhood cancer
Cancer in children is uncommon—it represents approximately 2% of all cancer cases. Nevertheless, after trauma, it is the second most common cause of death in children older than 1 year of age. Approximately 130 new cases of cancer are identified each year per million children younger than 15 years of age (about 1 in 7000). Therefore, the annual incidence of cancer in the United States includes 9000 children younger than 15 years age, with another 4000 patients being diagnosed with cancer
Normal development and growth
During normal development, cells evolve to perform highly specialized functions to meet the physiological needs of the organism. Development and growth involve tightly regulated processes that include continued cell proliferation, differentiation to specialized cell types, and programmed cell death (apoptosis). An intricate system of checks and balances ensures proper control over these physiological processes. The genetic composition (genotype) of a cell determines which pathway(s) will be
Malignant transformation
Alteration or inactivation of any of the components of normal cell regulatory pathways may lead to the dysregulated growth that is the hallmark of neoplastic cells. Malignant transformation may be characterized by the failure of cells to differentiate or cellular dedifferentiation, increased invasiveness and metastatic capacity, and decreased drug sensitivity. Tumorigenesis reflects the accumulation of excess cells that results from increased cell proliferation and decreased apoptosis or
Epigenetic alterations
As stated previously, the hallmark of cancer is dysregulated gene expression. However, not only do genetic factors influence gene expression but epigenetic factors do as well, with these factors being at least as important as genetic changes in their contribution to the pathogenesis of cancer. Epigenetic alterations are defined as those heritable changes in gene expression that do not result from direct changes in DNA sequence. Mechanisms of epigenetic regulation most commonly include DNA
Heredity and childhood cancer
Advances in molecular genetic techniques have improved our understanding of cancer predisposition syndromes. Constitutional genetic abnormalities present in all cells of the body that are hereditary (ie, passed from parent to child) or nonhereditary (ie, de-novo mutations in the sperm or oocyte before fertilization) contribute to an estimated 10% to 15% of pediatric cancers.31 Constitutional chromosomal abnormalities are the result of an abnormal number or structural rearrangement of the normal
Conclusions
Advances in basic cancer research in the past 3 decades have led to an increased understanding of the genetic and epigenetic events in the pathogenesis and progression of human malignancies, including those of childhood. Several pediatric malignancies serve as models for the investigative approach to cancer, highlighting the utility of molecular analysis for a variety of purposes. Demonstration of tumor-specific translocations by cytogenetics, fluorescence in situ hybridization, and reverse
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