Interphase Cytogenetics: At the Interface of Genetics and Morphology

Cancer is a genetic disease caused by chromosomal aberrations and gene mutations, which propel normal cells into uncontrolled growth, invasiveness and metastases formation. Because chromosomal and genetic alterations impact tumour aggressiveness, therapy response, and prognosis their detection in clinical samples (e.g., fine needle aspirates and bioptic material) plays an increasingly critical role in individualized disease management. In situ hybridization with genetic markers to tumour specimen, a concept coined “Interphase Cytogenetics” [3] allows one to visualize chromosomal alterations in intact cell nuclei. Both numerical and structural chromosomal aberrations can be visualized using suitable probes or probe cocktails. The growing knowledge on tumour specific genetic and chromosomal aberrations can therefore be translated to diagnostic pathology. The identification and validation of such biomarkers will be greatly accelerated by highthroughput analysis tools such as cDNA-arrays for the analysis of differentially expressed messages [5] and tissues arrays [14] for the simultaneous screening of the expression pattern of hundreds of different tumours (see Fig. 1). The detection of chromosome and gene alterations in interphase nuclei of cytological specimens and tis-