Pediatric oncology

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Cancer is a disease whose progression is driven by a series of accumulating genetic and epigenetic changes influenced by hereditary factors and the somatic environment. These changes result in individual cells acquiring a phenotype that provides those cells with a survival advantage over surrounding normal cells. Our understanding of the processes that occur in malignant transformation is increasing, with many discoveries in cancer cell biology having been made through the study of childhood tumors. The processes involved in oncogenesis and cancer progression will be discussed in this review.

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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

References (43)

  • W.A. Bleyer

    The impact of childhood cancer on the United States and the world

    CA Cancer J Clin

    (1990)
  • Y. Kaneko et al.

    Different karyotypic patterns in early and advanced stage neuroblastomas

    Cancer Res

    (1987)
  • A.T. Look et al.

    Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma

    N Engl J Med

    (1984)
  • W.A. May et al.

    Ewing sarcoma 11; 22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation

    Proc Natl Acad Sci U S A

    (1993)
  • W.A. May et al.

    The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1

    Mol Cell Biol

    (1993)
  • P.H. Sorensen et al.

    A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG

    Nat Genet

    (1994)
  • N. Galili et al.

    Fusion of a fork head domain gene to Pax3 in the solid tumour alveolar rhabdomyosarcoma

    Nat Genet

    (1993)
  • F.G. Barr

    The role of chimeric paired box transcription factors in the pathogenesis of pediatric rhabdomysarcoma

    Cancer Res

    (1999)
  • P.H. Sorensen et al.

    Pax3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: A report from the Children's Oncology Group

    J Clin Oncol

    (2002)
  • Y. Chen et al.

    Mutations of the PTPN11 and RAS genes in rhabdomyosarcoma and pediatric hematological malignancies

    Genes Chromosomes Cancer

    (2006)
  • W. Lutz et al.

    Conditional expression of N-myc in human neuroblastoma cells increases expression of alpha-prothymosin and ornithine decarboxylase and accelerates progression into S-phase early after mitogenic stimulation of quiescent cells

    Oncogene

    (1996)
  • Cited by (0)

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