Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition

BTeV : an experiment to measure mixing, CP violation, and rare decays of beauty and charm at the Fermilab collider.

We discuss the physics goals and rationale for a detector to study Beauty and Charm decays in the forward direction at the Fermilab Tevatron Collider. We then describe the BTeV detector which has been designed to achieve these goals and present its physics reach based on extensive simulation. We conclude by comparing BTeV to other experiments designed to explore similar topics

New FOCUS results on charm mixing and CP violation

We present a summary of recent results on CP violation and mixing in the charm quark sector based on a high statistics sample collected by photoproduction experiment FOCUS (E831 at Fermilab). We have measured the difference in lifetimes for the D0 decays: D0 --> K-pi+ and D0 --> K-K+ . This translates into a measurement of the y_cp mixing parameter in the D0/D0bar system, under the assumptions that K+K- is an equal mixture of CP odd and CP even eigenstates, and CP violation is negligible in the neutral charm meson system. We verified the latter assumption by searching for a CP violating asymmetry in the Cabibbo suppressed decay modes D+ --> K-K+pi+ , D0 --> K-K+ and D0 --> pi-pi+ . We show preliminary results on a measurement of the branching ratio Gamma(D*+ --> pi+(K+pi-))/Gamma(D*+ --> pi+(K-pi+))

Preliminay results on charmed meson spectroscopy.

We report the preliminary measurement by the FOCUS Collaboration (E831 at Fermilab) of masses and widths of the L=1 charm mesons D*0_2 and D*+_2. The fit of the invariant mass distribution requires an additional term to account for a broad structure over background