Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We carried out a mutational analysis of 3,594 genes coding for cell surface proteins (Surfaceome) in 23 colorectal cancer cell lines, searching for new altered pathways, druggable mutations and mutated epitopes for targeted therapy in colorectal cancer. A total of 3,944 somatic non-synonymous substitutions and 595 InDels, occurring in 2,061 (57%) Surfaceome genes were catalogued. We identified 48 genes not previously described as mutated in colorectal tumors in the TCGA database, including genes that are mutated and expressed in >10% of the cell lines (SEMA4C, FGFRL1, PKD1, FAM38A, WDR81, TMEM136, SLC36A1, SLC26A6, IGFLR1). Analysis of these genes uncovered important roles for FGF and SEMA4 signaling in colorectal cancer with possible therapeutic implications. We also found that cell lines express on average 11 druggable mutations, including frequent mutations (>20%) in the receptor tyrosine kinases AXL and EPHA2, which have not been previously considered as potential targets for colorectal cancer. Finally, we identified 82 cell surface mutated epitopes, however expression of only 30% of these epitopes was detected in our cell lines. Notwithstanding, 92% of these epitopes were expressed in cell lines with the mutator phenotype, opening new venues for the use of "general" immune checkpoint drugs in this subset of patients.
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PMID:Mutational analysis of genes coding for cell surface proteins in colorectal cancer cell lines reveal novel altered pathways, druggable mutations and mutated epitopes for targeted therapy. 2519 53

Exfoliation syndrome (XFS) is an age-related systemic disorder of the extracellular matrix with important ocular manifestations. In this disorder, exfoliation material (XFM) is deposited in the anterior chamber of the eye on the lens, iris, ciliary body, as well as other intraocular structures. This accumulation of XFM can obstruct the trabecular meshwork, resulting in elevated intraocular pressure and eventually causing glaucomatous optic neuropathy. In itself a highly hereditable condition, XFS is also the commonest recognizable cause of open-angle glaucoma worldwide, accounting for a majority of cases in some countries. Outside the eye, XFM deposits around blood vessels, particularly in association with elastic connective tissue, are found in numerous organs, including the skin, heart, and lungs. Long suspected to be a genetic disorder on the basis of familial aggregation studies, recent genome-wide association studies uncovered strong association between 7 genetic loci (LOXL1, CACNA1A, FLT1-POMP, TMEM136-ARHGEF12, AGPAT1, RBMS3, and SEMA6A) and increased risk of XFS. At the same time, a lower than usual sibling relative risk for XFS compared with other inherited conditions suggests XFS to be a complex disorder. The evidence to date suggests that additional genetic loci and biological insights for XFS remain to be identified through larger studies.
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PMID:Genetics of Exfoliation Syndrome. 2996 97