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Defining Genetic Intra-Tumor Heterogeneity: A Chronological Annotation Of Mutational Pathways, Wentao Luo, Fan Wu, Susan R. Atlas, Gavin Pickett, Kimberly K. Leslie, Donghai Dai

Kimberly K. Leslie

Tumor heterogeneity is believed to be important in tumor progression and its response to therapies. However, despite numerous mutations being reported in human tumors, genetic intra-tumor heterogeneity remains poorly defined. We have developed a novel strategy to provide a chronological annotation of mutational events in a tumor. We used an endometrial tumor from a patient and transplanted it into athymic mice to create many tumor xenografts. While the patient tumor xenografts were initially responsive to raloxifene treatment, xenografts created with cancer cell clones isolated from the same patient tumor showed dramatic differences in response to raloxifene, indicating existence of intra-tumor …