Abstract
Abstract Intratumor diversity for hereditary traits is the driver of tumor evolution, including disease progression and therapeutic resistance. To investigate the role of intratumor genetic and phenotypic heterogeneity in breast tumor progression and in therapeutic responses, we performed immunoFISH (iFISH) analyses of distant metastases from the same patient and breast tumor biopsies before and after treatment. iFISH allows for the combined analysis of phenotypic markers (e.g., such as CD24 and CD44) and chromosomal copy number gains at the single-cell level. In each tumor we evaluated four distinct tumor cell populations (CD44+/CD24-, CD44-/CD24+, CD44+/CD24+, and CD44-/CD24- cells) for chromosomal gain at 8q24 and other commonly gained chromosomal regions. iFISH data was evaluated using ecological and evolutionary models. We found high degree of genetic heterogeneity within and between the four different cell subpopulations in some tumors, in some patients the distant metastases were highly divergent, and the degree of intratumor diversity was altered by treatment and was associated with clinical characteristics. Our findings demonstrate the power of analyzing tumors as ecosystems and indicate that numerical measures of intratumor diversity can be used as clinically useful biomarkers predicting the risk of progression and therapeutic resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr PL03-03. doi:10.1158/1538-7445.AM2011-PL03-03
Published Version
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