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Free keywords:
cancer evolution; oncogenes; mutation fitness; BCR-ABL; cancer dynamics
Abstract:
Mutations in oncogenes and tumor suppressor genes confer a fitness advantage to cells that can lead to cancer. The tumor phenotype normally results from the interaction of many mutant genes making it difficult to estimate the fitness advantage provided by any oncogene, except when tumors depend on one oncogene only. We utilize a model of chronic myeloid leukemia (CML), to quantitate the fitness advantage conferred by expression of BCR-ABL in hematopoietic cells from in vivo patient data. We show that BCR-ABL expression provides a high fitness advantage, which explains why this single mutation drives the chronic phase of CML.