Next-generation sequencing (NGS) can reveal targetable mutations and aid diagnosis for patients with cancer of unknown primary, according to study results published in The Oncologist

NGS revealed an actionable mutation in 57% of patients studied and helped provide a site-specific diagnosis for 15% of patients.

This retrospective study included data from 40 patients with cancer of unknown primary who underwent genomic profiling by NGS in 2020-2021 at a large community hospital in Canada.

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The median age of the cohort was 70 (range, 42-85) years, and 57% of patients were women. Most patient samples (72%) were classified as carcinoma not otherwise specified, and 17% were adenocarcinoma. Tumor burden was located mostly above the diaphragm in 65% of cases.

All NGS was performed with the Oncomine Precision Assay GX, a 50-gene panel including hotspot DNA analysis, copy-number assessment, and RNA fusion panel. The turnaround time of NGS was a median of 3 business days, and the failure rate was 0%.

Researchers found at least 1 genetic alteration in 80% of patients (n=32). The genes that most commonly harbored alterations were KRAS (35%), CDKN2A (15%), TP53 (15%), and ERBB2 (12%). 

An actionable mutation was found in 57% of patients (n=23). The genes that most commonly harbored actionable mutations were KRAS, CDKN2A, ERBB2, FGFR3, and PIK3CA

For 6 patients (15%), NGS results prompted further investigation that led to a site-specific diagnosis. Two patients were found to have HER2-positive breast carcinoma, 2 had desmoid fibromatosis, 1 had intrahepatic cholangiocarcinoma, and 1 had metastatic midline NUT carcinoma. 

“We demonstrate the feasibility of a rapid point-of-care molecular profiling test to be integrated as part of routine histopathology diagnostics,” the researchers concluded. “Furthermore, more than half of the patients had an actionable alteration identified, providing further evidence that molecular profiling should be part of the standard of care for patients diagnosed with cancer of unknown primary.” 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Wang X, Beharry A, Sheffield BS, Cheema PK. Feasibility of point-of-care genomic profiling in the diagnosis and treatment of cancer of unknown primary. Oncologist. Published online March 18, 2023. doi:10.1093/oncolo/oyad054