scholarly journals Accurate calling of KIAA1549‐BRAF fusions from DNA of human brain tumours using methylation array‐based copy number and gene panel sequencing data

2020 ◽  
Author(s):  
Damian Stichel ◽  
Daniel Schrimpf ◽  
Philipp Sievers ◽  
Annekathrin Reinhardt ◽  
Abigail K. Suwala ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tumours ◽  
Copy Number ◽  
Gene Panel ◽  
Sequencing Data ◽  
Methylation Array ◽  
Human Brain Tumours ◽  
Gene Panel Sequencing ◽  
Panel Sequencing

scholarly journals PATH-11. PROSPECTIVE (EPI-)GENETIC CLASSIFICATION OF > 1,000 PEDIATRIC CNS TUMORS—THE MNP 2.0 STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii426-iii426
Author(s):  
Dominik Sturm ◽  
Felix Sahm ◽  
Felipe Andreiuolo ◽  
David Capper ◽  
Marco Gessi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Panel ◽  
Cns Tumors ◽  
Lower Grade ◽  
High Grade ◽  
Sequencing Data ◽  
Cns Tumor ◽  
Gene Panel Sequencing ◽  
Tumor Entities ◽  
Panel Sequencing

Abstract The large variety of CNS tumor entities affecting children and adolescents, some of which are exceedingly rare, results in very diverging patient outcomes and renders accurate diagnosis challenging. To assess the diagnostic utility of routine DNA methylation-based CNS tumor classification and gene panel sequencing, the Molecular Neuropathology 2.0 study prospectively integrated these (epi-)genetic analyses with reference neuropathological diagnostics as an international trial for newly-diagnosed pediatric patients. In a four-year period, 1,215 patients with sufficient tissue were enrolled from 65 centers, receiving a reference neuropathological diagnosis according to the WHO classification in >97%. Using 10 FFPE sections as input, DNA methylation analysis was successfully performed in 95% of cases, of which 78% with sufficient tumor cell content were assigned to a distinct epigenetic tumor class. The remaining 22% did not match any of 82 represented classes, indicating novel rare tumor entities. Targeted gene panel sequencing of >130 genes performed for 96% of patients with matched blood samples detected diagnostically, prognostically, or therapeutically relevant somatic alterations in 48%. Germline DNA sequencing data indicated potential predisposition syndromes in ~10% of patients. Discrepant results by neuropathological and epigenetic classification (29%) were enriched in histological high-grade gliomas and implicated clinical relevance in 5% of all cases. Clinical follow-up suggests improved survival for some patients with high-grade glioma histology and lower-grade molecular profiles. Routine (epi-)genetic profiling at the time of primary diagnosis adds a valuable layer of information to neuropathological diagnostics and will improve clinical management of CNS tumors.

scholarly journals Assessment of tumor mutation burden calculation from gene panel sequencing data

2019 ◽  
Vol Volume 12 ◽  
pp. 3401-3409 ◽  
Author(s):  
Zhenwu Xu ◽  
Jiawei Dai ◽  
Dandan Wang ◽  
Hui Lu ◽  
Heng Dai ◽  
...  
Keyword(s):  
Gene Panel ◽  
Sequencing Data ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Gene Panel Sequencing ◽  
Panel Sequencing

scholarly journals A Method to Evaluate the Quality of Clinical Gene-Panel Sequencing Data for Single-Nucleotide Variant Detection

2017 ◽  
Vol 19 (5) ◽  
pp. 651-658 ◽  
Author(s):  
Chung Lee ◽  
Joon S. Bae ◽  
Gyu H. Ryu ◽  
Nayoung K.D. Kim ◽  
Donghyun Park ◽  
...  
Keyword(s):  
Single Nucleotide Variant ◽  
Gene Panel ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Variant Detection ◽  
Gene Panel Sequencing ◽  
Panel Sequencing

Gene Panel Sequencing of Primary and Relapsed Pediatric T-ALL Shows That Relapse-Specific Mutations Are Diverse and Mostly Non-Recurrent

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1428-1428
Author(s):  
Paulina Pechanska ◽  
Joachim Kunz ◽  
Tobias Rausch ◽  
Obul Reddy Bandapalli ◽  
Elena Orlova ◽  
...  
Keyword(s):  
Copy Number ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Recognition Rate ◽  
Genetic Alterations ◽  
Gene Panel ◽  
Copy Number Alterations ◽  
Target Capture ◽  
Gene Panel Sequencing ◽  
Panel Sequencing

Abstract Precursor T-cell acute lymphoblastic leukemia (T-ALL) remains one of the major challenges of pediatric oncology, because relapses are frequently refractory to treatment and fatal. We aimed at identifying relapse specific genetic alterations by analyzing a cohort of 147 primary T-ALL patients and of 70 relapsed T-ALL patients with targeted gene panel sequencing. In addition to the analysis of single nucleotide variants (SNVs) and small insertions and deletions (InDels), we made use of the available coverage data to characterize aberrant copy number alterations (CNA). DNA from bone marrow of these 217 pediatric T-ALL patients was analyzed by gene panel sequencing after target capture with Agilent HaloPlex. In the target capture design, exons of 324 genes were included that had been found before by whole exome sequencing to carry somatic mutations in a pilot set of relapsed T-ALL or that have been reported to be mutated in T-ALL in the literature. We did not analyze corresponding remission samples and did not discriminate between germline and somatic alterations. Only mutations with an allele frequency (AF) > 10% were considered and absence of the mutation in the 1000 Genomes variant catalogue was required. Copy number analysis based on read-depth data identified deletions (DEL) and amplifications (AMP). Direct comparison of CNAs by multiplex ligation-dependent probe amplification (MPLA) and gene panel sequencing was possible for 13 overlapping regions covering 14 genes in 185 samples. Recognition rate by coverage analysis was 98% (256/260) for biallelic alterations and 81% (92/114) for monoallelic alterations found by MLPA. On average, gene panel sequencing identified 6.7 mutations in initial diagnosis samples (SNVs: 5.2; InDels: 1.5) and 7.9 mutations in relapse samples (SNVs: 5.9; InDels: 2). In the group of primary leukemia and relapse samples, the average AMP/DEL per patient was 8.2 (AMP: 3.2, DEL: 5.0) and 8.8 (AMP: 4.2, DEL: 4.6), respectively. 31 genes were found to be mutated and 46 deleted/amplified in 10 or more patients (see Table 1 and 2). Table 1. Most commonly mutated genes (SNVs and InDels) Gene Total # of mutations # pts with mutation in primary T-ALL(n=147) # pts with mutation in relapsed T-ALL (n=70) NOTCH1 178 88 (60%) 38 (54%) PHF6 47 24 (16%) 16 (23%) FBXW7 42 20 (14%) 17 (24%) OBSCN 35 20 (14%) 10 (14%) DNM2 28 17 (12%) 10 (14%) PTEN 34 20 (14%) 4 (6%) XIRP2 24 19 (13%) 5 (7%) CDH23 23 11 (7%) 11 (16%) WT1 36 11 (7%) 8 (11%) NT5C2 22 1 (1%) 17 (24%) Table 2. Most common copy number alterations Amplifications Deletions Gene primary T-ALL (n=147) relapsed T-ALL (n=64) Gene primary T-ALL (n=147) relapsed T-ALL (n=64) MYB 9 (6%) 9 (15%) CDKN2A 102 (70%) 36 (59%) MYC 11 (8%) 6 (10%) CDKN2B 83 (57%) 31 (51%) NRG1 11 (8%) 3 (5%) MLLT3 28 (19%) 5 (8%) UNC5D 11 (8%) 3 (5%) PHIP 18 (12%) 6 (10%) NCOA2 11 (8%) 3 (5%) ELOVL4 18 (12%) 5 (8%) PTK2B 11 (8%) 3 (5%) MAP3K7 17 (12%) 5 (8%) FDFT1 11 (8%) 3 (5%) CASP8AP2 17 (12%) 5 (8%) ABL1 8 (5%) 3 (5%) APC 19 (13%) 3 (5%) CNOT3 8 (5%) 3 (5%) LEF1 16 (11%) 5 (8%) SMG8 3 (2%) 7 (10%) PAX5 15 (10%) 5 (8%) Potential novel mechanisms of oncogene activation are amplifications of PTK2B, a gene that has been found to be deregulated by fusion in Philadelphia-like BCP-ALL and that is potentially targetable by tyrosine kinase inhibitors, and of MYC, which has long been known to be a key player in T-ALL leukemogenesis and that is amplified in neuroblastoma and medulloblastoma. Enriched in relapse, we identified mutations in NT5C2 (p=1.4E-08), TP53 (p=0.0006) and CCDC88A (p=0.01), and amplifications of a region on chr 17q represented by the genes CLTC, ABCA5, C17orf80 and SRSF2. MLLT3 deletions were enriched in primary samples (p=0.04), consistent with the observation that MLLT3 deletions confer a lower risk of relapse in patients treated on BFM protocols. Conclusion Gene panel sequencing emerges as a suitable tool for a comprehensive genetic characterization of pediatric T-ALL. Within the group of selected genes contained in the panel, CNA were as frequent as point mutations. Only few genes were found to be specifically altered in relapse, indicating that progression to relapse may involve diverse, non-recurrent genetic alterations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Matrilineal analysis of mutations in the DMD gene in a multigenerational South Indian cohort using DMD gene panel sequencing

2021 ◽  
Author(s):  
Arun Shastry ◽  
Sankaramoorthy Aravind ◽  
Meeta Sunil ◽  
Keerthi Ramesh ◽  
Berty Ashley ◽  
...  
Keyword(s):  
Gene Panel ◽  
South Indian ◽  
Dmd Gene ◽  
Gene Panel Sequencing ◽  
Panel Sequencing

scholarly journals NG2 expression regulates vascular morphology and function in human brain tumours

NeuroImage ◽  
2006 ◽  
Vol 29 (3) ◽  
pp. 965-976 ◽  
Author(s):  
C. Brekke ◽  
A. Lundervold ◽  
P.Ø. Enger ◽  
C. Brekken ◽  
E. Stålsett ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tumours ◽  
Vascular Morphology ◽  
Human Brain Tumours ◽  
And Function

scholarly journals Characterization of intellectual disability and autism comorbidity through gene panel sequencing

2019 ◽  
Vol 40 (9) ◽  
pp. 1346-1363 ◽  
Author(s):  
Maria C. Aspromonte ◽  
Mariagrazia Bellini ◽  
Alessandra Gasparini ◽  
Marco Carraro ◽  
Elisa Bettella ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Gene Panel ◽  
Gene Panel Sequencing ◽  
Panel Sequencing
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