IDH mutations have been identified in many tumor types, including glioma, acute myeloid leukemia, and cholangiocarcinoma, and testing for the mutation can be a valuable diagnostic and predictive biomarker. We identified melanomas with IDH mutations at a single institution and sought to further characterize this cohort. 405 melanoma cases collected at Massachusetts General Hospital between 2015 and 2017 underwent molecular characterization of 91 genes, including IDH1 and IDH2, by next generation sequencing. Demographic and primary site data were recorded. The mean age of the cohort was 69 years with 70% of patients male. An IDH mutation was identified in 20 cases of 405 tested tumors (4.9%). Seventeen of 20 mutant cases (85%) showed an IDH1(R132C) mutation, while the remaining three cases (15%) were hypermutant, with non-hotspot alterations of unknown significance. Of the 17 cases with an IDH1(R132C) mutation, 16 occurred in sun exposed areas (non-acral, nonmucosal) and 14/16 (88%) had co-occurring alterations in the MAPK pathway (BRAF, NRAS, MAPK3), a similar frequency compared to IDH wild-type melanomas in the cohort (329/385, 85%). Histology of 13 IDH1(R132C) mutant cases was reviewed, with 12 exhibiting an epithelioid growth pattern and one with mixed epithelioid and spindled patterns. All cases showed absence of or non-brisk tumor infiltrating lymphocytes. Of the 17 cases with IDH1(R132C) mutation, ten received immunotherapy. Two showed a reduction in tumor burden by imaging, and eight showed progression. At last follow-up (median follow-up time¼32.6 months), five patients were alive with no evidence of disease, nine were alive with disease, and three had died of disease. We identified a small cohort of melanomas that harbor IDH1 mutations with frequent co-existing MAPK mutations. This group represents a distinct molecular subgroup classification of melanoma. Limited data suggests these cases may have a poor response to immunotherapy.
Introduction: Vitamin C is a major antioxidant in plants and plays an important role in reducing the activity of reactive oxygen species. In humans, the main role of this molecule is the elimination of activity of active oxygen species along with being cofactor for many enzymes. Human is one of the few mammalian species that can not synthesize this vitamin and needs to get it through food sources. The GDP-Lgalactose phosphorylase (GGP) gene is one of the most important genes in the biosynthetic pathway of vitamin C, which codes for the GDPL-galactose phosphorylase enzyme. Isolation of GGP gene is an important step in transferring it to elevate vitamin C biosynthesis in plants. Materials and Methods: In current study, the isolation of this gene from kiwi plant was carried out and then was cloned in the pTG19-T plasmid via T/A cloning and subsequently sequenced to confirm it. Results: Sequencing analysis of the GGP gene showed that this fragment contains 1383 bp and the start and stop codons were ATG and TGA, respectively. The bioinformatics analysis of this gene can provide important information on gene and protein structure. The alignment of cloned sequence was done with other Actinidia DNA sequences. The results based on neighbor-joining alignment showed that some of the mutations in nucleotides were related to the third nucleotide in a specific codon. Also, the minimum distance of protein sequences was observed between isolated GGP and Actinidia chinensis. Conclusions: Based on analyses, isolated gene (GGP) can be used for increase vitamin C content in other plants such as cucumber and for resistance to environmental stresses in different plants.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.