0000000000531014
AUTHOR
David Weber
Comprehensive Genomic and Transcriptomic Analysis of Three Synchronous Primary Tumours and a Recurrence from a Head and Neck Cancer Patient
Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma (HNSCC) patients. Here, we analysed three synchronous primaries and a recurrence from one patient by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants that might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. The mutational signature analysis confirmed the impact of alc…
ArtiFuse—computational validation of fusion gene detection tools without relying on simulated reads
Abstract Motivation Gene fusions are an important class of transcriptional variants that can influence cancer development and can be predicted from RNA sequencing (RNA-seq) data by multiple existing tools. However, the real-world performance of these tools is unclear due to the lack of known positive and negative events, especially with regard to fusion genes in individual samples. Often simulated reads are used, but these cannot account for all technical biases in RNA-seq data generated from real samples. Results Here, we present ArtiFuse, a novel approach that simulates fusion genes by sequence modification to the genomic reference, and therefore, can be applied to any RNA-seq dataset wit…
Integrative analysis of structural variations using short-reads and linked-reads yields highly specific and sensitive predictions.
Genetic diseases are driven by aberrations of the human genome. Identification of such aberrations including structural variations (SVs) is key to our understanding. Conventional short-reads whole genome sequencing (cWGS) can identify SVs to base-pair resolution, but utilizes only short-range information and suffers from high false discovery rate (FDR). Linked-reads sequencing (10XWGS) utilizes long-range information by linkage of short-reads originating from the same large DNA molecule. This can mitigate alignment-based artefacts especially in repetitive regions and should enable better prediction of SVs. However, an unbiased evaluation of this technology is not available. In this study, w…
An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors.
A one-two, CAR-T cell punch Chimeric antigen receptor (CAR)–T cells have been clinically effective in killing certain hematological malignancies, but achieving long-term patient responses for solid tumors remains a challenge. Reinhard et al. describe a two-part “CARVac” strategy to overcome poor CAR-T cell stimulation and responses in vivo. They introduce the tight junction protein claudin 6 (CLDN6) as a new CAR-T cell target and designed a nanoparticulate RNA vaccine encoding a chimeric receptor directed toward CLDN6. This lipoplex RNA vaccine promotes CLDN6 expression on the surface of dendritic cells, which in turn stimulates and enhances the efficacy of CLDN6-CAR-T cells for improved tu…