Genome Sequencing Outperforms Exome Sequencing in Formalin-Fixed Paraffin Embedded Tumors Leading to Improved...

Precision oncology is based on comprehensive molecular characterization of a patient's tumor. This is mostly realized by next-generation sequencing panels or exome sequencing. Data on the value of genome sequencing from formalin-fixed paraffin embedded (FFPE) material in a clinical setting is still scarce. In this pilot, we generated datasets of matched exome and genome sequencing of FFPE tumor samples from 15 cancer patients to benchmark quality metrics, clinical feasibility, and added value for a molecular tumor board. Despite the reduced sequencing depth, diagnostic detection of small nucleotide variations, copy number variations, and complex biomarkers was maintained in genome sequencing compared to exome sequencing with the exception of hard-to-sequence regions. Evaluation by the local molecular tumor board identified additional treatment recommendations with high priority in 20% (3/15) of patients and additional molecular markers to support existing treatment recommendations in another 20% (3/15) of patients. Our work underscores the diagnostic superiority of genome sequencing even for FFPE samples and therefore supports its integration into clinical practice.