Deciphering the origin and therapeutic targets of cancer of unknown primary: a case report that illustrates the power of integrative whole-exome and transcriptome sequencing analysis.

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP.

Characteristics of bacterial and yeast microbiomes in spontaneous and mixed-fermentation beer and cider.

The production of experimental beer and cider products has increased, worldwide. The complex microbiomes found in these beverages affect their organoleptic qualities and chemical compositions and can have diverse impacts on human health. The total diversity of a microbiome can be elucidated through the use of high-throughput sequencing and comprehensive data analysis tools. We analysed the bacterial and yeast microbiomes found in mixed and spontaneously fermented beers (n = 14) and unpasteurised apple ciders (n = 6), using high-throughput 16S rRNA and internal transcribed spacer (ITS) sequencing. The ratio of bacteria to yeast was measured using quantitative polymerase chain reaction (qPCR), and short-chain organic acids were analysed using high-performance liquid chromatography (HPLC). An upgraded version of the Knomics-Biota system was used to analyse the data. The microbiomes included both starter microorganisms and those that originate from the production environment and the raw materials. In addition to the common Saccharomyces and Brettanomyces, the yeast diversity included many non-conventional species. The bacterial community in beer was dominated by Lactobacillus species, whereas these communities were more diverse in cider. Lactobacillus acetotolerans was prevalent in wild ales, whereas Candida ethanolica was prevalent in cask-matured beverages. We observed complex patterns of subspecies-level yeast diversity across beer styles, breweries, and countries. Our study represents an exploratory analysis of non-conventional beer and cider microbiomes and metabolomes, which contributes information necessary to develop improved quality control processes and may drive innovative product development in experimental and artisanal brewing.