RNA-Seq for the detection of gene fusions in solid tumors: development and validation of the JAX FusionSeq™ 2.0 assay

2022 ◽  
Author(s):  
Daniel Bergeron ◽  
Harshpreet Chandok ◽  
Qian Nie ◽  
Matthew Prego ◽  
Melissa Soucy ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Gene Fusions ◽  
Rna Seq ◽  
Development And Validation

scholarly journals Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2476 ◽  
Author(s):  
Shaoli Das ◽  
Kevin Camphausen ◽  
Uma Shankavaram
Keyword(s):  
Immune Function ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Data Sets ◽  
Cancer Type ◽  
Rna Seq ◽  
Prognostic Signature ◽  
Cell Functions ◽  
Cancer Types ◽  
Disease Free

To elucidate the role of immune cell infiltration as a prognostic signature in solid tumors, we analyzed immune-function-related genes from four publicly available single-cell RNA-Seq data sets and twenty bulk tumor RNA-Seq data sets from The Cancer Genome Atlas (TCGA). Unsupervised clustering of pan-cancer transcriptomic signature showed two major immune function types: one related to NK-, T-, and B-cell functions and the other related to monocyte, macrophage, dendritic cell, and Toll-like receptor functions. Kaplan–Meier analysis showed differential prognosis of these two groups, dependent on the cancer type. Our analysis of TCGA solid tumors with an elastic net model identified 155 genes associated with disease-free survival in different tumor types with varied influence across different cancer types. With this gene set, we computed cancer-specific prognostic immune score models for individual cancer types that predicted disease-free and overall survival. Validation of our model on available published data of immune checkpoint blockade therapies on melanoma, kidney renal cell carcinoma, non-small cell lung cancer, gastric cancer and bladder cancer confirmed that cancer-specific higher immune scores are associated with response to immunotherapy. Our analysis provides a comprehensive map of cancer-specific immune-related prognostic gene sets that are associated with immunotherapy response.

scholarly journals Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors

Neoplasia ◽  
2015 ◽  
Vol 17 (4) ◽  
pp. 385-399 ◽  
Author(s):  
Daniel H. Hovelson ◽  
Andrew S. McDaniel ◽  
Andi K. Cani ◽  
Bryan Johnson ◽  
Kate Rhodes ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Next Generation ◽  
Development And Validation ◽  
Generation Sequencing

Identification of RNA-Seq Gene Fusions in Ovarian Cancer

2016 ◽  
Vol 143 (1) ◽  
pp. 218
Author(s):  
G. Hsieh ◽  
L. Szabo ◽  
S. MacLaughlan ◽  
J. Salzman
Keyword(s):  
Ovarian Cancer ◽  
Gene Fusions ◽  
Rna Seq

Gene fusions evidence in a KIT/PDGFRA wild-type GIST without mutations in SDH units identified by a whole transcriptome study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e21523-e21523
Author(s):  
Milena Urbini ◽  
Annalisa Astolfi ◽  
Valentina Indio ◽  
Maristella Saponara ◽  
Margherita Nannini ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Surgical Removal ◽  
Erk Pathway ◽  
Gene Fusions ◽  
Rna Seq ◽  
Wild Type ◽  
Rna Pol Ii ◽  
Molecular Events ◽  
Frame Fusion ◽  
Whole Transcriptome

e21523 Background: A subset of KIT/PDGFRA wild-type GIST (WT) harbour mutations in SDH units. In the majority of the remaining cases of WT GIST no other molecular events are identified.We performed a RNA-seq in a WT GIST without mutations in SDH genes using next generation approach to discover molecular events in this GIST population. Methods: In 2003, a 63-year old woman underwent surgery for an ileal GIST (size 6 cm, MI 6/50HPF).After 6 years, she developed a recurrence with a single hepatic lesion. The KIT and PDGFRA analysis of the lesion did not show mutations. Therefore, she did not receive imatinib but she underwent a surgical removal. The analysis of all SDH units did not show mutations. So paired-end RNA-seq (75X2) was performed with Illumina HiScanSQ platform. After mapping the short reads on the human genome(HG19), SNVs and InDels were called by SNVMix2 with an accurate filtering procedures including predictors of mutations effect at protein level. Gene fusions discovery was done considering the agreement between DeFuse, ChimeraScan and FusionMap tools and validated by SangerSequencing using primers spanning the mRNA breakpoints. Results: Four different gene fusions and 206 non-synonymous SNVs were discovered, of which 62 were called deleterious by at least one predictor, and they are undergoing further validation. SPRED2-NELFCD gene fusion originated from an interchromosomal translocation-inversion between chr 20 and 2. The event involved exon1 of SPRED2 and exon11 of NELFCD, probably leading to inactivation of both genes. NELFCD encodes a component of the NELF complex that negatively regulates transcription elongation by RNA pol II, while SPRED2 is a member of the Sprouty /SPRED family that repress growth factor-induced activation of the MAPK/ERK pathway. The other three events were intrachromosomal aberrations: MARK2-PPFIA1 and PLA2G16-ATL3 on chr 11 and ASCC1-C10orf11 on chr 10. Only the first event led to an in-frame fusion (MARK2 ex1- PPFIA1 ex2) probably dysregulating the expression of the downstream gene. Conclusions: This is the first evidence of gene fusions in GIST. The oncogenetic role and the tumor frequency of these events deserve to be studied.

RNA-Seq analysis of glioma tumors to reveal targetable gene fusions.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2019-2019 ◽  
Author(s):  
Deepa Suresh Subramaniam ◽  
Joanne Xiu ◽  
Shwetal Mehta ◽  
Zoran Gatalica ◽  
Jeffrey Swensen ◽  
...  
Keyword(s):  
Life Sciences ◽  
Gene Fusions ◽  
Astrocytic Tumors ◽  
Fusion Genes ◽  
Rna Seq ◽  
Wild Type ◽  
Oligodendroglial Tumors ◽  
Grade Ii ◽  
Glioma Tumors ◽  
Grade Iii

2019 Background: Fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. We aim to use RNA-sequencing to interrogate a large cohort of gliomas for targetable genetic fusions. Methods: Gliomas were profiled using the ArcherDx FusionPlex Assay at a CLIA-certified lab (Caris Life Sciences) and 52 gene targets were analyzed. Fusions with preserved kinase domains were investigated. Results: Among 404 gliomas tested, 39 (9.7%) presented potentially targetable fusions, of which 24/226 (11%) of glioblastoma (GBM), 5/42 (12%) of anaplastic astrocytoma (AA), 2/25 (8%) of grade II astrocytoma and 3 of 7 (43%) of pilocytic astrocytoma (PA) harbored targetable fusions. In GBMs, 1 of 15 (6.7%) IDH-mutated tumors had a fusion while 22 of 175 (12.6%) IDH-wild type tumors had fusions. 46 oligodendroglial tumors were profiled and no fusions were seen, which was lower than frequency of fusions in astrocytic tumors (34/300, p = 0.0236). The most frequent fusions seen involved FGFR3 (N = 12), including 10 FGFR3-TACC3 (1 AA, 6 GBM and 3 glioma NOS); 1 FGFR3-NBR1 (AA) and 1 FGFR3-BRAP (GBM). 11 fusions involving MET were seen, 10 in GBM and 1 in AA. The most common MET fusion was PTPRZ1-MET (1 in AA and 4 in GBM), followed by ST7-MET (N = 3, GBM), CAPZA2-Met (N = 2, GBM) and TPR-MET (N = 1, GBM). 8 NTRK fusions were seen; 1 involving NTRK1 (BCAN-NTRK1, PA), 6 NTRK2 (1 NOS1AP-NTRK2 in AA; GKAP1-NTRK2, KCTD8-NTRK2, TBC1D2-NTRK2 and SOSTM1-NTRK2, 1 each in GBM and 1 VCAN-NTRK2 in grade II astrocytoma) and 1 NTRK3 (EML4-NTRK3 in GBM). EGFR fusions (2 EGFR-SEPT14 and 1 EGFR-VWC2) were seen in 3 GBMs, BRAF in 3 (1 KIAA1549-BRAF, 1 LOC100093631-BRAF in PA and 1 ZSCAN23-BRAF in glioma NOS) and PDGFRA (RAB3IP-PDGFRA, in GBM) in 1. C11orf95-RELA fusions were seen in 2 of 3 grade III ependymomas but not in the 2 grade II ependymomas. Conclusions: We report targetable fusion genes involving NTRK, MET, EGFR, FGFR3, BRAF and PDGFRA including novel fusions that haven’t been previously described in gliomas (e.g., EGFR-VWC2; FGFR3-NBR1). Fusions were seen in over 10% of astrocytic tumors, while none was seen oligodendrogliomas. Identification of such kinase-associated fusion transcripts may allow us to exploit therapeutic opportunities with targeted therapies in gliomas.

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