Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

Measurement and QCD analysis of double-differential inclusive jet cross sections in pp collisions at √s=8 TeV and cross section ratios to 2.76 and 7 TeV

A measurement of the double-differential inclusive jet cross section as a function of the jet transverse momentum pT and the absolute jet rapidity |y| is presented. Data from LHC proton-proton collisions at √ s = 8 TeV, corresponding to an integrated luminosity of 19.7 fb−1 , have been collected with the CMS detector. Jets are reconstructed using the anti-kT clustering algorithm with a size parameter of 0.7 in a phase space region covering jet pT from 74 GeV up to 2.5 TeV and jet absolute rapidity up to |y| = 3.0. The low-pT jet range between 21 and 74 GeV is also studied up to |y| = 4.7, using a dedicated data sample corresponding to an integrated luminosity of 5.6 pb−1 . The measured jet cross section is corrected for detector effects and compared with the predictions from perturbative QCD at next-to-leading order (NLO) using various sets of parton distribution functions (PDF). Cross section ratios to the corresponding measurements performed at 2.76 and 7 TeV are presented. From the measured double-differential jet cross section, the value of the strong coupling constant evaluated at the Z mass is αS(MZ) = 0.1164+0.0060 −0.0043, where the errors include the PDF, scale, nonperturbative effects and experimental uncertainties, using the CT10 NLO PDFs. Improved constraints on PDFs based on the inclusive jet cross section measurement are presented