10 research outputs found

    Truncated FGFR2 is a clinically actionable oncogene in multiple cancers.

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    Somatic hotspot mutations and structural amplifications and fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2) occur in multiple types of cancer1. However, clinical responses to FGFR inhibitors have remained variable1-9, emphasizing the need to better understand which FGFR2 alterations are oncogenic and therapeutically targetable. Here we apply transposon-based screening10,11 and tumour modelling in mice12,13, and find that the truncation of exon 18 (E18) of Fgfr2 is a potent driver mutation. Human oncogenomic datasets revealed a diverse set of FGFR2 alterations, including rearrangements, E1-E17 partial amplifications, and E18 nonsense and frameshift mutations, each causing the transcription of E18-truncated FGFR2 (FGFR2ΔE18). Functional in vitro and in vivo examination of a compendium of FGFR2ΔE18 and full-length variants pinpointed FGFR2-E18 truncation as single-driver alteration in cancer. By contrast, the oncogenic competence of FGFR2 full-length amplifications depended on a distinct landscape of cooperating driver genes. This suggests that genomic alterations that generate stable FGFR2ΔE18 variants are actionable therapeutic targets, which we confirmed in preclinical mouse and human tumour models, and in a clinical trial. We propose that cancers containing any FGFR2 variant with a truncated E18 should be considered for FGFR-targeted therapies

    In situ recording of Mars soundscape

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    International audiencePrior to the Perseverance rover landing, the acoustic environment of Mars was unknown. Models predicted that: (i) atmospheric turbulence changes at centimeter scales or smaller at the point where molecular viscosity converts kinetic energy into heat, (ii) the speed of sound varies at the surface with frequency and (iii) high frequency waves are strongly attenuated with distance in CO2. However, theoretical models were uncertain because of a lack of experimental data at low pressure, and the difficulty to characterize turbulence or attenuation in a closed environment. Here using Perseverance microphone recordings, we present the first characterization of Mars’ acoustic environment and pressure fluctuations in the audible range and beyond, from 20 Hz to 50 kHz. We find that atmospheric sounds extend measurements of pressure variations down to 1,000 times smaller scales than ever observed before, revealing a dissipative regime extending over 5 orders of magnitude in energy. Using point sources of sound (Ingenuity rotorcraft, laser-induced sparks), we highlight two distinct values for the speed of sound that are ~10 m/s apart below and above 240 Hz, a unique characteristic of low-pressure CO2-dominated atmosphere. We also provide the acoustic attenuation with distance above 2 kHz, allowing us to elucidate the large contribution of the CO2 vibrational relaxation in the audible range. These results establish a ground truth for modelling of acoustic processes, which is critical for studies in atmospheres like Mars and Venus ones

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

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