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Detection of sequential genetic alterations relevant for breast cancer development.

Breast cancer emerges as a multistep process with transformation of normal cells via steps of hyperplasia, premalignant change and in situ carcinoma. 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 histological sections is needed to correlate the specific histological change 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 polymorphisms detecting differences in short tandem repeat sequences are much more informative than standard two-allele restriction fragment length polymorphism markers. Still, the direct correlation of the genetic alterations to specific histological findings is the key to reveal insight into tumour biology and thereby gain prognostic information for the individual breast cancer patient.