The preliminary results seen with entrectinib in the Phase I studies of patients with NTRK / ROS1 / ALK fusions have led to the initiation of an open-label, multicenter, global, Phase 2 basket study ( STARTRK-2 ) to examine the use of entrectinib in patients having tumors with these gene rearrangements.
22.
The ability of T cells to recognize foreign antigens is mediated by the T cell receptor ( TCR ), which is a surface protein able to recognize short protein sequences ( peptides ) that are presented on MHC . The purpose of thymocyte development is to produce mature T cells with a diverse array of functional T cell receptors, through the process of TCR gene rearrangement.
23.
In patients with NSCLC, approximately 2 % are positive for a " ROS1 " gene rearrangement, and these rearrangements are mutually exclusive of " ALK " rearrangement . " ROS1 " fusion-positive patients tend to be younger, with a median age of 49.8 years, and never-smokers, with a diagnosis of adenocarcinoma.
24.
The key disadvantage in a gene rearrangement process for T cell receptors is that by random chance, some arrangements of gene fragments will create a T cell receptor capable of binding self-peptides presented on MHC class I or MHC class II . If T cells bearing these T cell receptors were to enter the periphery, they would be capable of activating an immune response against self, resulting in autoimmunity.
25.
Secondary structure models for mt-tmRNAs . ( A ) The two-piece tmRNA in oomycetes and jakobids except J . libera, After removing the intervening sequence ( Int .; dashed ark ) by RNA processing enzymes, the two resulting RNA pieces ( blue and red lines ) remain together through base pairing . ( B ) The standard one-piece tmRNA in J . libera that most likely emerged secondarily through gene rearrangement.
26.
This study found that tumors harboring these NTRK1 gene rearrangements did not have somatic mutations in other oncogenes like " KRAS, NRAS, " or " PIK3CA, " and both fusion proteins were shown to be oncogenic, as their expression in NIH3T3 cells resulted in transformation and tumor formation in nude mice . 10 ?In a sampling of 140 Spitzoid neoplasms, which included 75 Spitz naevi, 32 atypical Spitz tumors, and 33 Spitzoid melanomas, " NTRK1 " rearrangements were detected in a total of 16.4 % of the samples ( 23 patients ), with 8, 8, and 7 patients harboring rearrangements in the respective tumor types.
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