EZH2 alterations in follicular lymphoma: biological and clinical correlations

International audienceThe histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n = 55) and H3K27 methylation (n = 63) profiles were also evaluated. In total, 37% of patients (59/159) harbored an alteration in the EZH2 gene (mutation n = 46, gain n = 23). Both types of alterations were associated with highly similar transcriptional changes, with increased proliferation programs. An H3K27me3/me2 IHC score fully distinguished mutated from wild-type samples, showing its applicability as surrogate for EZH2 mutation analysis. However, this score did not predict the presence of gains at the EZH2 locus. The presence of an EZH2 genetic alteration was an independent factor associated with a longer progression-free survival (hazard ratio 0.58, 95% confidence interval 0.36–0.93, P = 0.025). We propose that the copy-number status of EZH2 should also be considered when evaluating patient stratification and selecting patients for EZH2 inhibitor-targeted therapies

Models of habituation in infancy

Research on infant cognition using habituation methods has sparked considerable controversy in recent years. At the core of the debates is the issue of whether infants have early (and possibly innate) conceptual understandings. This article reviews a range of computational models of habituation that might provide insights into such discussions. The models are assessed against key behavioral and neural features of habituation: temporal unfolding, exponential decrease, familiarity-to-novelty shift, habituation to repeated testing, discriminability of habitual items, selective inhibition and cortical–subcortical interactions. The review suggests that current models fail to offer comprehensive explanations of the behavioral phenomena

An interacting systems model of infant habituation

& Habituation and related procedures are the primary behavioral tools used to assess perceptual and cognitive competence in early infancy. This article introduces a neurally constrained computational model of infant habituation. The model combines the two leading process theories of infant habituation into a single functional system that is grounded in functional brain circuitry. The HAB model (for Habituation, Autoassociation, and Brain) proposes that habituation behaviors emerge from the opponent, complementary processes of hippocampal selective inhibition and cortical long-term potentiation. Simulations of a seminal experiment by Fantz [Visual experience in infants: Decreased attention familiar patterns relative to novel ones. Science, 146, 668–670, 1964] are reported. The ability of the model to capture the fine detail of infant data (especially age-related changes in performance) underlines the useful contribution of neurocomputational models to our understanding of behavior in general, and of early cognition in particular. &amp