Clustered Genomic Alterations in Chromosome 7p Dictate Outcomes and Targeted Treatment Responses of Lung Adenocarcinoma With EGFR-Activating Mutations

Purpose Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been proven more effective for patients with lung adenocarcinoma with EGFR-activating mutation rather than wild type, the former group still includes approximately 30% nonresponders. The molecular basis of this substantial response heterogeneity is unknown. Our purpose was to seek molecular aberrations contributing to disease progression at the genome-wide level and identify the prognostic signature unique to patients with EGFR-activating mutation. Patients and Methods We first investigated the molecular differences between tumors with EGFR-activating mutation and wild-type tumors by conducting high-density array comparative genomic hybridization on a collection of 138 adenocarcinoma tissues. We then used an independent group of 114 patients to validate the clinical relevance of copy-number alterations (CNAs) in predicting overall and disease-free survival. Finally, focusing on 23 patients with EGFR mutation receiving EGFR-TKI treatment, we investigated the association between CNAs and response to EGFR-TKIs. Results We identified chromosome regions with differential CNAs between tumors with EGFR-activating mutation and wild-type tumors and found the aberration sites to cluster highly on chromosome 7p. A cluster of six representative chromosome 7p genes predicted overall and disease-free survival for patients with EGFR-activating mutation but not for those with wild type. Importantly, simultaneous presence of more genes with increased CNAs in this cluster correlated with less favorable response to EGFR-TKIs in patients with EGFR-activating mutation. Conclusion Our results shed light on why responses to EGFR-TKIs are heterogeneous among patients with EGFR-activating mutation. They may lead to better patient management in this population. J Clin Oncol 29:3435-3442. (C) 2011 by American Society of Clinical Oncolog

Beam Test Performance Studies of CMS Phase-2 Outer Tracker Module Prototypes

International audienceA new tracking detector will be installed as part of the Phase-2 upgrade of the CMS detector for the high-luminosity LHC era. This tracking detector includes the Inner Tracker, equipped with silicon pixel sensor modules, and the Outer Tracker, consisting of modules with two parallel stacked silicon sensors. The Outer Tracker front-end ASICs will be able to correlate hits from charged particles in these two sensors to perform on-module discrimination of transverse momenta $p_\mathrm{T}$. The $p_\mathrm{T}$ information is generated at a frequency of 40 MHz and will be used in the Level-1 trigger decision of CMS. Prototypes of the so-called 2S modules were tested at the Test Beam Facility at DESY Hamburg between 2019 and 2020. These modules use the final front-end ASIC, the CMS Binary Chip (CBC), and for the first time the Concentrator Integrated Circuit (CIC), optical readout and on-module power conversion. In total, seven modules were tested, one of which was assembled with sensors irradiated with protons. An important aspect was to show that it is possible to read out modules synchronously. A cluster hit efficiency of about 99.75% was achieved for all modules. The CBC $p_\mathrm{T}$ discrimination mechanism has been verified to work together with the CIC and optical readout. The measured module performance meets the requirements for operation in the upgraded CMS tracking detector

Measurement of the fractional radiation length of a pixel module for the CMS Phase-2 upgrade via the multiple scattering of positrons

International audienceHigh-luminosity particle collider experiments such as the ones planned at the High-Luminosity Large Hadron Collider require ever-greater vertexing precision of the tracking detectors, necessitating also reductions in the material budget of the detectors. Traditionally, the fractional radiation length ($x/X_0$) of detectors is either estimated using known properties of the constituent materials, or measured in dedicated runs of the final detector. In this paper, we present a method of direct measurement of the material budget of a CMS prototype module designed for the Phase-2 upgrade of the CMS detector using a 40-65 MeV positron beam. A total of 630 million events were collected at the Paul Scherrer Institut PiE1 experimental area using a three-plane telescope consisting of the prototype module as the central plane, surrounded by two MALTA monolithic pixel detectors. Fractional radiation lengths were extracted from scattering angle distributions using the Highland approximation for multiple scattering. A statistical technique recovered runs suffering from trigger desynchronisation, and several corrections were introduced to compensate for local inefficiencies related to geometric and beam shape constraints. An overall average $x/X_0$ of (0.84 $\pm$ 0.10)% across the surveyed regions was measured, which is compatible with an empirical estimate of 0.825% computed from known material properties. Higher-granularity maps of the fractional radiation length were produced for both rectangular regions and regions of uniform material composition. The results bode well for the CMS Phase-2 upgrade modules, which will play a key role in the minimisation of the material budget of the upgraded detector