BAP1 loss defines a new class of renal cell carcinoma

The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of monoubiquitinated histone 2A lysine 119 (H2AK119ub1). BAP1 loss sensitizes RCC cells in vitro to genotoxic stress. Notably, mutations in BAP1 and PBRM1 anticorrelate in tumors (P = 3 × 10(-5)), and combined loss of BAP1 and PBRM1 in a few RCCs was associated with rhabdoid features (q = 0.0007). BAP1 and PBRM1 regulate seemingly different gene expression programs, and BAP1 loss was associated with high tumor grade (q = 0.0005). Our results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.     

Indication of drier periods on Mars from the chemistry and mineralogy of atmospheric dust

The ubiquitous atmospheric dust on Mars is well mixed by periodic global dust storms, and such dust carries information about the environment in which it once formed and hence about the history of water on Mars. The Mars Exploration Rovers have permanent magnets to collect atmospheric dust for investigation by instruments on the rovers. Here we report results from M?ssbauer spectroscopy and X-ray fluorescence of dust particles captured from the martian atmosphere by the magnets. The dust on the magnets contains magnetite and olivine; this indicates a basaltic origin of the dust and shows that magnetite, not maghemite, is the mineral mainly responsible for the magnetic properties of the dust. Furthermore, the dust on the magnets contains some ferric oxides, probably including nanocrystalline phases, so some alteration or oxidation of the basaltic dust seems to have occurred. The presence of olivine indicates that liquid water did not play a dominant role in the processes that formed the atmospheric dust.