Oncogenic gene fusions are important drivers in many cancer types, including carcinomas, with diagnostic and therapeutic implications. Hence, sensitive and rapid methods for parallel profiling in formalin-fixed and paraffin-embedded (FFPE) specimens are needed. In this study we analyzed gene fusions in a cohort of 517 cases where standard treatment options were exhausted. To this end the Archer DX Solid tumor panel (AMP; 285 cases) and the Oncomine Comprehensive Assay v3 (OCA; 232 cases) were employed. Findings were validated by Sanger sequencing, fluorescence in situ hybridization (FISH) or immunohistochemistry. Both assays demonstrated minimal dropout rates (AMP: 2.4%; = 7/292, OCA: 2.1%; = 5/237) with turnaround times of 6-9 working days (median, OCA and AMP, respectively). Hands-on-time for library preparation was 6 h (AMP) and 2 h (OCA). We detected = 40 fusion-positive cases (7.7%) with TMPRSS2::ERG in prostate cancer being most prevalent ( = 9/40; 22.5%), followed by other gene fusions identified in cancers of unknown primary ( = 6/40; 15.0%), adenoid cystic carcinoma ( = 7/40; 17.5%), and pancreatic cancer ( = 7/40; 17.5%). Our results demonstrate that targeted RNA-sequencing of FFPE samples is feasible, and a well-suited approach for the detection of gene fusions in a routine clinical setting.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769558 | PMC |
| http://dx.doi.org/10.3390/cancers11091309 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pediatric Soft Tissue Sarcoma in Limb-Girdle Muscular Dystrophy: Molecular Findings and Clinical Implications.
Am J Case Rep
December 2024
Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
BACKGROUND Limb-girdle muscular dystrophy recessive 1 (LGMDR1) is an autosomal recessive degenerative muscle disorder characterized by progressive muscular weakness caused by pathogenic variants in the CAPN3 gene. Desmoplastic small round cell tumors (DSRCT) are ultra-rare and aggressive soft tissue sarcomas usually in the abdominal cavity, molecularly characterized by the presence of a EWSR1::WT1 fusion transcript. Mouse models of muscular dystrophy, including LGMDR1, present an increased risk of soft tissue sarcomas.
View Article and Find Full Text PDFWhole genome and transcriptome analysis of pancreatic acinar cell carcinoma elucidates mechanisms of homologous recombination deficiency and unravels novel relevant fusion events.
Pathol Res Pract
December 2024
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, 413 East 69th Street, New York, NY 10021, USA. Electronic address:
Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor with a heterogeneous clinical course and, except for radical surgery, limited treatment options. We present a comprehensive study encompassing whole-genome and RNA sequencing of 7 tumor samples from 3 metastatic PACC patients to further delineate its genomic landscape and potential therapeutic implications. Our findings reveal distinct signatures of homologous recombination deficiency (HRD) in patients harboring pathogenic germline BRCA1/2 and FANCL mutations, demonstrating favorable responses to poly (ADP-ribose) polymerase 1 (PARP) inhibitors with prolonged disease-free intervals.
View Article and Find Full Text PDFTransgenic tomato strategies targeting whitefly eggs from apoplastic or ovary-directed proteins.
BMC Plant Biol
December 2024
Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
Background: Transgenic plants expressing proteins that target the eggs of the ubiquitous plant pest Bemisia tabaci (whitefly) could be an effective insecticide strategy. Two approaches for protein delivery are assessed using the mCherry reporter gene in transgenic tomato plants, while accommodating autofluorescence in both the plant, phloem-feeding whitefly and pedicle-attached eggs.
Results: Both transgenic strategies were segregated to homozygous genotype using digital PCR.
Annotating protein functions via fusing multiple biological modalities.
Commun Biol
December 2024
College of Computer Science and Technology, Ocean University of China, Qingdao, China.
Understanding the function of proteins is of great significance for revealing disease pathogenesis and discovering new targets. Benefiting from the explosive growth of the protein universal, deep learning has been applied to accelerate the protein annotation cycle from different biological modalities. However, most existing deep learning-based methods not only fail to effectively fuse different biological modalities, resulting in low-quality protein representations, but also suffer from the convergence of suboptimal solution caused by sparse label representations.
View Article and Find Full Text PDFTransduction of jellyfish superoxide dismutase mediated by TAT peptide ameliorates HO-induced oxidative stress in HaCaT cells.
Sci Rep
December 2024
Naval Special Medical Center, Naval Medical University, Shanghai, 200433, China.
Superoxide dismutase (SOD) plays important roles in the balance of oxidation and antioxidation in body mostly by scavenging superoxide anion free radicals (O). Previously, we reported a novel Cu/Zn SOD from jellyfish Cyanea capillata, named CcSOD1, which exhibited excellent SOD activity and high stability. TAT peptide is a common type of cell penetrating peptides (CPPs) that efficiently deliver extracellular biomacromolecules into cytoplasm.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!