Whole genome sequencing improves tissue-of-origin diagnosis and treatment options for cancer of unknown primary
Journal Title
Nature Communications
Publication Type
Research article
Abstract
Genomics can inform both tissue-of-origin (TOO) and precision treatments for patients with cancer of unknown primary (CUP). Here, we use whole genome and transcriptome sequencing (WGTS) for 72 patients and show diagnostic superiority of WGTS over panel testing (386-523 genes) in 71 paired cases. WGTS detects all reportable DNA features found by panel as well as additional mutations of diagnostic or therapeutic relevance in 76% of cases. Curated WGTS features and a CUP prediction algorithm (CUPPA) trained on WGTS data of known cancer types informs TOO in 71% of cases otherwise undiagnosed by clinicopathology review. WGTS informs treatments for 79% of patients, compared to 59% by panel testing. Finally, WGS of cell-free DNA (cfDNA) from patients with a high cfDNA tumour fraction (>7%), enables high-likelihood CUPPA predictions in 41% of cases. WGTS is therefore superior to panel testing, broadens treatment options, and is feasible using routine pathology samples and cfDNA.
Publisher
Springer Nature
Keywords
Humans; *Neoplasms, Unknown Primary/genetics/diagnosis/therapy; *Whole Genome Sequencing/methods; Female; Male; Mutation; Algorithms; Middle Aged; Genomics/methods; Aged; Transcriptome; Biomarkers, Tumor/genetics; Gene Expression Profiling
Department(s)
Pathology; Medical Oncology; Laboratory Research
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-025-59661-x
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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