A_longitudinal_study_of_tumour_progression_in_a_mouse_model_of_breast_cancer

Recent comparative transcriptomic analyses have shown that breast cancer GEMMs can reflect molecular subtypes of human breast cancer. We have generated primary mouse mammary tumors by tissue specific overexpression of Gli1 on a C57BL/6 x FVB cross. Primary tumors were serially transplanted for 10 generations in NOD/SCID immunocompromised mice and the primary and generation 10 tumors from 4 series were assayed using Agilent gene expression microarrays. In addition, capillary sequencing of a small panel of genes identified recurrent Kras (G12V) mutations. The gene expression analysis showed a clear representation of luminal, basal and mesenchymal subtypes among the 8 analyzed samples. Comparisons between primary and generation 10 tumors within each series showed a plasticity in tumor genetics as well as in tumor subtype where primary luminal tumors shifted to basal and primary basal shifted to more mesenchymal/claudin-low characteristics. As our preliminary results indicate tumor subtype evolution to more aggressive phenotypes in the late tumor generations we aim at also investigating aberrations on the genomic level by whole exome Next Generation sequencing.