Cytogenetic clues to breast carcinogenesis

The somatic mutation theory of cancer maintains that tumorigenesis is drive n by genetic alterations, many of which are visible cytogenetically. We hav e examined breast cancer by chromosome banding analysis after short-term cu lturing of tumor cells and here review our findings in 322 karyotypically a bnormal samples obtained since: 1992 from 256 patients. The screening capab ilities of this technique enabled us to identify several cytogenetic subgro ups of breast cancer, to study the intratumor heterogeneity of breast carci nomas, and to compare primary tumors with their metastases. Using chromosom e abnormalities as clonality markers, we could determine on an individual b asis when multiple,! ipsilateral or bilateral breast, tumors were independe nt de novo carcinomas and when they resulted from the spreading of a single malignant clone within one breast or from one breast to the other. The dis tribution of chromosomal breakpoints and genomic gains and losses is clearl y nonrandom in breast cancer, something that can guide further investigatio ns using molecular methods. Based on the total dataset, we propose a multip athway model of mammary carcinogenesis that takes into consideration the ge netic heterogeneity revealed by the karyotypic findings and review the kary otypic-pathologic correlations and the possible clinical applications of th e cytogenetic knowledge. (C) 2002 Wiley-Liss, Inc.