20 research outputs found
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Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy
Adolescent Bipolar Disorder: A Clinical Vignette
Adolescence is a vulnerable developmental phase marked by physical, psychological, and social changes that rapidly expose young people to a wide range of new stressors. When differentiating between bipolar disorder and teenage “acting out,” a careful history is important. Adolescent bipolar disorder is a psychiatric illness characterized by fluctuating episodes of mood elevation and depression that is frequently neither recognized nor formally diagnosed. Adolescents with bipolar disorder often manifest a more nonepisodic, chronic course with continuous rapid-cycling patterns than do adults. Pharmacologic treatment of adolescent bipolar disorder is difficult and often requires combination therapy to address comorbidities like attention-deficit/hyperactivity disorder and anxiety disorder. Adjuncts to pharmacologic treatment of bipolar disorder can be beneficial. Psychosocial treatments include family education, enhanced parenting techniques, stress management, and the development of effective coping strategies