DETECTION OF SEQUENTIAL GENETIC ALTERATIONS RELEVANT FOR BREAST-CANCER DEVELOPMENT

Breast cancer emerges as a multistep process with transformation of no rmal cells via steps of hyperplasia, premalignant change and in situ c arcinoma, Cytogenetic and molecular genetic analyses of breast cancer samples indicate that tumour development involves the accumulation of various genetic alterations, including amplification of oncogenes and mutation or loss of tumour suppressor genes. Microdissection of histol ogical sections is needed to correlate the specific histological chang e and the genetic alteration. For detection of oncogene amplification quantitative differential polymerase chain reaction (PCR) can. be used , For assessment of loss of heterozygosity PCR-based microsatellite po lymorphisms detecting differences in short tandem repeat sequences are much more informative than standard two-allele restriction fragment l ength polymorphism markers, Still, the direct correlation of the genet ic alterations to specific histological findings is the key to reveal insight into tumour biology and thereby gain prognostic information fo r the individual breast cancer patient.