The RUNX/CBFß Complex in Breast Cancer: A Conundrum of Context.

Dissecting and identifying the major actors and pathways in the genesis, progression and aggressive advancement of breast cancer is challenging, in part because neoplasms arising in this tissue represent distinct diseases and in part because the tumors themselves evolve. This review attempts to illustrate the complexity of this mutational landscape as it pertains to the RUNX genes and their transcription co-factor CBFß. Large-scale genomic studies that characterize genetic alterations across a disease subtype are a useful starting point and as such have identified recurring alterations in CBFB and in the RUNX genes (particularly RUNX1). Intriguingly, the functional output of these mutations is often context dependent with regards to the estrogen receptor (ER) status of the breast cancer. Therefore, such studies need to be integrated with an in-depth understanding of both the normal and corrupted function in mammary cells to begin to tease out how loss or gain of function can alter the cell phenotype and contribute to disease progression. We review how alterations to RUNX/CBFß function contextually ascribe to breast cancer subtypes and discuss how the in vitro analyses and mouse model systems have contributed to our current understanding of these proteins in the pathogenesis of this complex set of diseases.

Experimental evolution of local parasite maladaptation.

Sign and magnitude of local adaptation in host-parasite systems may vary with ecological, epidemiological or genetic parameters. To investigate the role of host genetic background, we established long-term experimental populations of different genotypes of the protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. We observed the evolution of an overall pattern of parasite local maladaptation for infectivity, indicating a general coevolutionary disadvantage of this parasite. Maladaptation extended to host populations with the same genetic background, similar to extending from the local to a higher regional level in natural populations. Patterns for virulence were qualitatively similar, but with less statistical support. A nonsignificant correlation with levels of (mal)adaptation for infectivity suggests independent evolution of these traits. Our results indicate similar (co)evolutionary trajectories in populations with different genetic backgrounds. Nonetheless, the correlated clines of genetic distance and parasite performance illustrate how genetic background can shape spatial gradients of local adaptation.