Advanced Genomic Testing Enhances Treatment and Diagnosis in Cancers of Unknown Primary

A recent groundbreaking study demonstrates the significant role of whole genome and transcriptome sequencing (WGTS) in improving diagnostic precision and expanding treatment options for patients with cancers of unknown primary (CUP). Published in Nature Communications, this research was led by Associate Professor Richard Tothill from the Rare Disease Oncogenomics Lab at the Collaborative Center for Genomic Cancer Medicine, a partnership between the University of Melbourne and Peter MacCallum Cancer Centre.

The study involved a comparison between WGTS and traditional gene panel testing in a retrospective cohort of 72 CUP patients. Cancer of unknown primary is characterized by metastatic tumors where the original cancer site cannot be identified through standard diagnostics. It accounts for approximately 1%–3% of all new cancer cases and generally poses a poor prognosis, with limited treatment options.

Findings reveal that WGTS detects all reportable mutations identified by conventional panel testing while also uncovering additional clinically relevant features in 76% of cases. This comprehensive analysis involves examining a patient's entire DNA and RNA, providing insights into known cancer-driving mutations that could be targeted with specific therapies. Importantly, WGTS suggested potential treatment strategies for 79% of patients, enabling 24% more patients to become eligible for standard treatments or phase I–II clinical trials.

A crucial advantage of WGTS is its ability to determine the tissue of origin of CUP tumors. Using advanced diagnostic features and the CUP prediction algorithm (CUPPA), trained on extensive WGTS data, the study achieved a 77% success rate in identifying the tissue of origin. This outperformed conventional methods which only succeeded in 34% of cases, providing a new pathway for targeted treatment approaches.

The feasibility of WGTS on archived formalin-fixed paraffin-embedded (FFPE) tissue samples and cell-free DNA was also demonstrated, with a 97% success rate on preserved samples and a 41% likelihood of detecting tissue of origin from liquid biopsies. These developments could greatly improve access to precision diagnostics, especially in regional areas where fresh tissue collection is challenging.

Overall, this research highlights the potential of WGTS to revolutionize the diagnosis and treatment of CUP patients by offering more accurate tissue of origin identification and personalized therapy options, ultimately improving patient outcomes. Continued validation and integration of these genomic tools could lead to more equitable and effective cancer care.

Source: https://medicalxpress.com/news/2025-05-genomic-aids-precision-therapy-tissue.html