Artikel
Chromosomal alterations in head and neck cancer: Window to the biology of disease
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Veröffentlicht: | 24. April 2006 |
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Gliederung
Text
Cytogenetic alterations underlie the development of squamous cell carcinomas of the head and neck (SCCHN) and most other tumors. Since many of the molecular genetic changes in SCCHN result from chromosomal alterations, a complete perspective on the molecular genetic changes in tumors requires a basic introduction to the cytogenetic alterations in SCCHN, their molecular correlates and clinical implications. The most frequent cytogenetic alterations in SCCHN are gains of 3q, 8q, 9q, 20q, 7p, 11q13, and 5p and losses of 3p, 9p, 21q, 5q, 13q, 18q, and 8p. The mechanismus by which many of these cytogenetic aberrations arise have been predicted, and some are under investigation. For example, gene amplification involving chromosomal band 11q13, which occurs in nearly half of SCCHN and is associated with a poor prognosis, appears to occur via breakage-fusion-bridge cycles, possibly initiated at chromosomal fragile sites by tobacco smoke-induced DNA double strand breaks. Thus, cytogenetic analysis is valuable for placing the molecular genetic findings in perspective at the cellular level. Further, cytogenetic endpoints may be useful tools for dissecting clinical differences in tumor behavior and response to therapy. Numerous studios are underway to examine the biology of and genetic alterations in SCCHN which will lead to additional markers for use as rapid, noninvasive screening methods for individuals at high risk for primary or recurrent SCCHN. The goal of our research is to minimize morbidity and mortality from SCCHN by identifying useful predictors of disease and recurrence risk and response to therapy, in order to implement earlier detection and more effective prevention and/or treatment strategies.