The use of cytogenetics and molecular cytogenetic analysis in hematology has both increased and improved over the last decade. Fluorescence in situ hybridization (FISH) has been incorporated into most diagnostic laboratories to complement chromosome analysis and further improve its accuracy. In the era of risk-adapted and mutation-directed therapy, accurate assessment of genetic status is of paramount importance. In many current studies, patients are stratified on the basis of their cytogenetic or molecular rearrangements, since numerous disease- or subtype-specific abnormalities have independent prognostic outcomes. Such is the specificity of certain chromosomal rearrangements that molecular cytoge-netic information can provide an unequivocal diagnosis of the type of malignancy. This is true for both leukemia and lymphoma, although the number of recurrent chromosomal changes identified in leukemia exceeds that in lymphoma. Nevertheless, a number of highly specific lymphoma-associ-ated changes have diagnostic and therapeutic value. In national treatment trials in the UK, such as those run by the Medical Research Council for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), cytogenetic information is vital to treatment stratification, and in other diseases, such as chronic lymphoblastic leukemia and myeloma, the impact of chromosomal abnormalities is beginning to be recognized.
Chromosomal analysis of metaphase cells provides a global assessment of karyotype and still plays a major role in modern tumor cytogenetics. FISH is used as a rapid, sensitive test to complement G-band analysis, allowing the detection of cryptic or subtle changes. In addition, FISH can be used to screen non-dividing cell populations, such as bone marrow smears, tumor imprints and paraffin-embedded tissue sections (PETS). A vast array of FISH probes is currently available, aimed at detecting fusion genes, numerical abnormalities, chromosomal imbalance, chromosomal rearrangement and complex events. FISH has been further developed to allow the global detection of tumor-associated gain and loss using tumor DNA as a FISH probe against normal metaphase chromosomes. This technique is known as 'comparative genomic hybridization' (CGH) and in turn has led to the very recent technique of array CGH. Array CGH promises to provide much higher resolution of genomic imbalance compared with chromosome-based CGH. Currently, custom-designed arrays containing oncogenes and tumor suppressor genes are available commercially and arrays with DNA clones spaced at 1 Mb intervals throughout the genome are becoming available. Gene expression profiling also offers exciting prospects in hematology and, coupled with the molecular cytogenetic and cytogenetic information, accurate diagnostic genetic analysis looks set to revolutionize patient management.
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