Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

Thuijl, Hinke F. van; Scheinin, Ilari; Sie, Daoud; Alentorn, Agustí; Essen, Hendrik F. van; Cordes, Martijn; Fleischeuer, Ruth; Gijtenbeek, Anja; Beute, Guus; Brink, W. A. van den; Meijer, Gerrit A.; Havenith, Miek G.; Idbaïh, Ahmed; Hoang-Xuân, Khê; Mokhtari, Karima; Verhaak, Roel G.W.; Valk, Paul van der; Wiel, Mark A. van de; Heimans, Jan J.; Aronica, Eleonora; Reijneveld, Jaap C.; Wesseling, Pieter; Ylstra, Bauke

doi:10.1186/preaccept-1419175304135559

Cited by 11 publications

(20 citation statements)

References 23 publications

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“…Shallow WGS and alignment to the reference genome Shallow WGS was performed with DNA isolated from FFPE sections of 15 LGGs (van Thuijl et al 2014), two oral squamous cell carcinomas (SCCs AB042 and AB052) (Bhattacharya et al 2011), and the breast cancer cell line BT474 on the Illumina HiSeq 2000 using run mode SR50, which sequences only one end of the DNA molecules for 50 base pairs. In general, these DNA samples were multiplexed with others so that each HiSeq sequencing lane contained between 18 and 22 total samples.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to the existing user-definable parameters available in DNAcopy, an option to smooth signals over a specified number of consecutive bins has been added in QDNAseq. For calling (annotation of segments with copy number states such as gain, amplification, or loss), the package CGHcall (van de Wiel et al 2007) can be invoked at the user's discretion. (Miller et al 2011) and FREEC (Boeva et al 2011).…”

Section: The Software Package Qdnaseqmentioning

confidence: 99%

“…Fifteen LGGs (van Thuijl et al 2014), two SCCs (Bhattacharya et al 2011), and the breast cancer cell line BT474 were used to develop and illustrate the shallow WGS pipeline presented. All material used from LGG and SCC tumors was derived from FFPE archival samples.…”

Section: Sample Selectionmentioning

confidence: 99%

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DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly

et al. 2014

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Detection of DNA copy number aberrations by shallow whole-genome sequencing (WGS) faces many challenges, including lack of completion and errors in the human reference genome, repetitive sequences, polymorphisms, variable sample quality, and biases in the sequencing procedures. Formalin-fixed paraffin-embedded (FFPE) archival material, the analysis of which is important for studies of cancer, presents particular analytical difficulties due to degradation of the DNA and frequent lack of matched reference samples. We present a robust, cost-effective WGS method for DNA copy number analysis that addresses these challenges more successfully than currently available procedures. In practice, very useful profiles can be obtained with~0.13 genome coverage. We improve on previous methods by first implementing a combined correction for sequence mappability and GC content, and second, by applying this procedure to sequence data from the 1000 Genomes Project in order to develop a blacklist of problematic genome regions. A small subset of these blacklisted regions was previously identified by ENCODE, but the vast majority are novel unappreciated problematic regions. Our procedures are implemented in a pipeline called QDNAseq. We have analyzed over 1000 samples, most of which were obtained from the fixed tissue archives of more than 25 institutions. We demonstrate that for most samples our sequencing and analysis procedures yield genome profiles with noise levels near the statistical limit imposed by read counting. The described procedures also provide better correction of artifacts introduced by low DNA quality than prior approaches and better copy number data than high-resolution microarrays at a substantially lower cost.

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Section: Resultsmentioning

confidence: 99%

Section: The Software Package Qdnaseqmentioning

confidence: 99%

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DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly

et al. 2014

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“…A majority of the samples have been used in previous studies (Supplementary Table S2)[29, 56]. Tumor samples were fresh-frozen or formalin fixed paraffin embedded (FFPE) tissues.…”

Section: Methodsmentioning

confidence: 99%

“…For each sample, an area was delineated that contained >60% tumor cells. The corresponding area on subsequent sections of 10 µm was used for DNA isolation extracted with the QIAGEN FFPE DNA extraction kit[56]. …”

Section: Methodsmentioning

confidence: 99%

Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment

et al. 2015

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Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment naïve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ treated, hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.

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IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas

et al. 2015

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Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II–III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and wild-type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR)=1.21, 95% confidence interval (CI)=0.91–1.61] compared to IDH-wild type tumors (HR=1.74, 95% CI=0.95–3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p<0.0001, HR=4.41, 95% CI=2.55–7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p=0.5157, HR=1.10, 95% CI=0.80–1.51), and could demonstrate a statistical interaction (p<0.0001) between IDH mutation and mitotic index (i.e. suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II–III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II–III gliomas as independent entities.

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Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

Cited by 11 publications

References 23 publications

DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly

DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly

Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment

IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas

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