Novel CIC Point Mutations and an Exon-Spanning, Homozygous Deletion Identified in Oligodendroglial Tumors by a Comprehensive Genomic Approach Including Transcriptome Sequencing
| العنوان: | Novel CIC Point Mutations and an Exon-Spanning, Homozygous Deletion Identified in Oligodendroglial Tumors by a Comprehensive Genomic Approach Including Transcriptome Sequencing |
|---|---|
| المؤلفون: | Karl Hackmann, Barbara Klink, Evelin Schröck, Sophie Eisenreich, Rolf Bjerkvig, Janice M. Nigro, Matthias Platzer, Gabriele Schackert, Khalil Abou-El-Ardat, Jaime Alberto Campos Valenzuela, Karol Szafranski, Andreas Rump, Eva-Maria Gerlach, Lars Kaderali, Dietmar Krex |
| المصدر: | PLoS ONE, Vol 8, Iss 9, p e76623 (2013) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Male, Mutation rate, Science, Oligodendroglioma, Nonsense mutation, Astrocytoma, Biology, medicine.disease_cause, Frameshift mutation, Cohort Studies, Exon, medicine, Humans, Point Mutation, Missense mutation, Oligodendroglial Tumor, Alleles, Genetics, Mutation, Multidisciplinary, Sequence Analysis, RNA, Gene Expression Profiling, Point mutation, Homozygote, DNA Helicases, RNA-Binding Proteins, Exons, Genomics, Glioma, Sequence Analysis, DNA, Middle Aged, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Repressor Proteins, Medicine, Female, Chromosome Deletion, Research Article |
| الوصف: | Oligodendroglial tumors form a distinct subgroup of gliomas, characterized by a better response to treatment and prolonged overall survival. Most oligodendrogliomas and also some oligoastrocytomas are characterized by a unique and typical unbalanced translocation, der(1,19), resulting in a 1p/19q co-deletion. Candidate tumor suppressor genes targeted by these losses, CIC on 19q13.2 and FUBP1 on 1p31.1, were only recently discovered. We analyzed 17 oligodendrogliomas and oligoastrocytomas by applying a comprehensive approach consisting of RNA expression analysis, DNA sequencing of CIC, FUBP1, IDH1/2, and array CGH. We confirmed three different genetic subtypes in our samples: i) the "oligodendroglial" subtype with 1p/19q co-deletion in twelve out of 17 tumors; ii) the "astrocytic" subtype in three tumors; iii) the "other" subtype in two tumors. All twelve tumors with the 1p/19q co-deletion carried the most common IDH1 R132H mutation. In seven of these tumors, we found protein-disrupting point mutations in the remaining allele of CIC, four of which are novel. One of these tumors also had a deleterious mutation in FUBP1. Only by integrating RNA expression and array CGH data, were we able to discover an exon-spanning homozygous microdeletion within the remaining allele of CIC in an additional tumor with 1p/19q co-deletion. Therefore we propose that the mutation rate might be underestimated when looking at sequence variants alone. In conclusion, the high frequency and the spectrum of CIC mutations in our 1p/19q-codeleted tumor cohort support the hypothesis that CIC acts as a tumor suppressor in these tumors, whereas FUBP1 might play only a minor role. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24edf59a3ac3968ea9f12666b92d34ecTest https://doi.org/10.1371/journal.pone.0076623Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....24edf59a3ac3968ea9f12666b92d34ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|