We discovered a novel somatic gene fusion, CD74-NRG1 , by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifi cally found in tumors bearing the fusion ( P < 0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment. SIGNIFICANCE:CD74-NRG1 fusions may represent a therapeutic opportunity for invasive mucinous lung adenocarcinomas, a tumor with no effective treatment that frequently presents with multifocal unresectable disease. Cancer Discov; 4(4); 415-22.

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We solve infinite-dimensional stochastic differential equations (ISDEs) describing an infinite number of Brownian particles interacting via twodimensional Coulomb potentials. The equilibrium states of the associated unlabeled stochastic dynamics are the Ginibre random point field and Dyson's measures, which appear in random matrix theory. To solve the ISDEs we establish an integration by parts formula for these measures. Because the long-range effect of two-dimensional Coulomb potentials is quite strong, the properties of Brownian particles interacting with twodimensional Coulomb potentials are remarkably different from those of Brownian particles interacting with Ruelle's class interaction potentials. As an example, we prove that the interacting Brownian particles associated with the Ginibre random point field satisfy plural ISDEs. IntroductionConsider infinitely many Brownian particles X = (X i ) i∈N moving in R d interacting via the two-dimensional (2D) Coulomb potentials Ψ β :Then the stochastic dynamics X = (X i ) i∈N is described by the following infinitedimensional stochastic differential equation (ISDE):Here {B i } i∈N is a sequence of independent copies of d-dimensional Brownian motions and X = (X i ) i∈N is a continuous (R d ) N -valued process.

We investigate the construction of diffusions consisting of infinitely numerous Brownian particles moving in R d and interacting via logarithmic functions (two-dimensional Coulomb potentials). These potentials are very strong and act over a long range in nature. The associated equilibrium states are no longer Gibbs measures.We present general results for the construction of such diffusions and, as applications thereof, construct two typical interacting Brownian motions with logarithmic interaction potentials, namely the Dyson model in infinite dimensions and Ginibre interacting Brownian motions. The former is a particle system in R, while the latter is in R 2 . Both models are translation and rotation invariant in space, and as such, are prototypes of dimensions d = 1, 2, respectively. The equilibrium states of the former diffusion model are determinantal or Pfaffian random point fields with sine kernels. They appear in the thermodynamical limits of the spectrum of the ensembles of Gaussian random matrices such as GOE, GUE and GSE. The equilibrium states of the latter diffusion model are the thermodynamical limits of the spectrum of the ensemble of complex non-Hermitian Gaussian random matrices known as the Ginibre ensemble.INTERACTING BROWNIAN MOTIONS WITH LOG POTENTIALS 5 problem to prove the Markov property of their processes and identify these two processes. 2 We also refer to [5][6][7] and [19] for stochastic processes of one-dimensional infinite particle systems related to random matrices.As for two-dimensional infinite systems with logarithmic interactions, the construction of stochastic processes based on the explicit computation of space-time correlation functions has not been done. Techniques useful in one-dimension, such as applying the Karlin-McGregor formula, are no longer valid in two dimensions.Let us briefly explain the main idea. We introduce the notion of quasi-Gibbs measures as a substitution for Gibbs measures. These measures satisfy inequality (2.8) involving a (finite volume) Hamiltonian. Inequality (2.8) is sufficient for the closability of the Dirichlet forms and the construction of the diffusions.To obtain the above-mentioned inequality we control the difference of the infinite volume Hamiltonians instead of the Hamiltonian, itself. The key point of the control is the usage of the geometric property of the random point fields behind the dynamics. Indeed, although the difference still diverges for Poisson random fields and Gibbs measures with translation invariance, it becomes finite for random point fields such as Dyson random point fields and Ginibre random point fields. For these random point fields the fluctuations of particles are extremely suppressed because the logarithmic potentials are quite strong. This cancels the sum of the difference of the infinite-volume Hamiltonians.The organization of the paper is as follows. In Section 2, we describe the set-up and state the main results (Theorems 2.2 and 2.3). We first introduce the notion of quasi-Gibbs measures and give a general resul...

We construct infinite-dimensional Wiener processes with interactions by constructing specific quasi-regular Dirichlet forms. Our assumptions are very mild; accordingly, our results can be applied to singular interactions such as hard core potentials, Lennard-Jones type potentials, and Dyson's model. We construct nonequilibrium dynamics.

By analyzing a reasonably small number of genes, patients with adenocarcinoma could be stratified according to their prognosis. The prognostic model could be applicable to future decisions concerning treatment.

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