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Members of the epidermal growth factor receptor family (EGFR/Erb1, Erb2/HER2, ErbB3/HER3 and ErbB4/HER4) are key targets for inhibition in cancer therapy 1. Critical for activation is the formation of an asymmetric dimer by the intracellular kinase domains, in which the C-terminal lobe (C-lobe) of one kinase domain induces an active conformation in the(More)
To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes(More)
  • Ramaswamy Govindan, Li Ding, Malachi Griffith, Janakiraman Subramanian, Nathan D. Dees, Krishna L. Kanchi +15 others
  • 2012
We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel(More)
  • Ron Bose, Marcel Verheij, Adriana Haimovitz-Friedman, Kathleen Scotto, Zvi Fuks, Richard Kolesnick
  • 1995
The sphingomyelin pathway, which is initiated by sphingomyelin hydrolysis to generate the second messenger ceramide, signals apoptosis for tumor necrosis factor alpha, Fas, and ionizing radiation. In the present studies, the anticancer drug daunorubicin also stimulated ceramide elevation and apoptosis in P388 and U937 cells. Cell-permeable analogs of(More)
The Drug-Gene Interaction database (DGIdb) mines existing resources that generate hypotheses about how mutated genes might be targeted therapeutically or prioritized for drug development. It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially 'druggable' genes. DGIdb can be accessed at(More)
A major goal of cancer genome sequencing is to identify mutations or other somatic alterations that can be targeted by selective and specific drugs. dGene is an annotation tool designed to rapidly identify genes belonging to one of ten druggable classes that are frequently targeted in cancer drug development. These classes were comprehensively populated by(More)
MOTIVATION Several tools exist to identify cancer driver genes based on somatic mutation data. However, these tools do not account for subclasses of cancer genes: oncogenes, which undergo gain-of-function events, and tumor suppressor genes (TSGs) which undergo loss-of-function. A method which accounts for these subclasses could improve performance while(More)
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