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The evolution of mesenchymal tumor classification schemes has coincided with cytogenetic and molecular advances. Increasing recognition of the specific genetic abnormalities inherent in these tumors and the growing use of cytogenetic and molecular genetic procedures have aided in the formulation of a diagnosis and the resolution of cellular origin. Several of the genetic markers are also of prognostic value, and the importance of molecular testing for guiding targeted therapeutic strategies in mesenchymal neoplasia is emerging.
The objective of this chapter is to review recurrent or tumor-specific genetic events in mesenchymal neoplasms and discuss the cytogenetic and molecular cytogenetic approaches commonly used in clinical practice to identify them.
GENETIC EVENTS AND MOLECULAR PATHOLOGIC APPROACHES
Three common genetic approaches used to identify mesenchymal tumor-specific abnormalities include (1) conventional cytogenetic; (2) molecular cytogenetic (fluorescence in situ hybridization [FISH]); and, (3) reverse transcription-polymerase chain reaction (RT-PCR) analyses. Historically, many of the genetic abnormalities that have come to be recognized as tumor specific in sarcomas were first identified by conventional cytogenetic analysis. In turn, the initial cytogenetic evidence facilitated the cloning of many candidate genes involved in the pathogenesis of mesenchymal tumors. Cytogenetic analysis has provided clinicians with a valuable tool to supplement their diagnostic armamentarium. The addition of molecular cytogenetic (FISH) and molecular approaches (RT-PCR) has further enhanced the sensitivity and accuracy of detecting nonrandom chromosomal imbalances or structural rearrangements in sarcomas, including assessment in formalin-fixed, paraffin-embedded tissues.
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