Novel fusion genes and chimeric transcripts in ependymal tumors

Abstract

We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc.

A systematic screen of breast cancer patients’ exomes for retrotransposon insertions reveals disease associated genes

“…The second identified retrotransposition mediated event that destroys protein integrity is the UQCR10 transcript inserting into the C1orf194 coding sequence (creating a UQCR10 processed pseudogene). This polymorphic insertion has been previously observed [7,28] and was present in 7 of our 65 samples. The mutant allele is unable to produce normal C1orf194 protein, but we cannot exclude that the UQCR10 pseudogene is expressed as a recombinant mRNA leading to overproduction of UQCR10 protein since a near full length UQCR10 transcript (from c.-15 till polyA tail) inserted in the 5' coding region (c.58_70) of the C1orf194 gene in the same orientation (Table 1).…”

Childhood supratentorial ependymomas with YAP1‐MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features

“…Its biological significance was not clear since YAP1 is known to be involved in various genetic abnormalities such as amplifications in some tumors and fusions with different partner genes. In addition, several other fusions have been identified in ependymomas , some of which were not recurrent and some occurred on the RNA level without underlying DNA mutations. The recurrent YAP1‐MAMLD1 fusion has been demonstrated to occur on the genomic level , also confirmed in this study by FISH.…”

Expressed fusion gene landscape and its impact in multiple myeloma

“…With this strategy, an average of 5.5 fusions was found in the patients (range 0–41), very similar to that observed in MM cell lines (average 6.1). This number in MM is relatively small compared to other cancer types, for instance 49 fusions in ependymal tumors (range 34–74) 19 and 20 fusions per patient in colon carcinoma 20 but significantly higher than in pediatric B-cell precursor acute lymphoblastic leukemia (average 1 in the non-high hyperdiploid patients, the later harbor none 21 ). However, as in pediatric ALL, HHMM, and hypodiploid patients exhibit less fusions than others.…”