Genomic Sequencing Offers Diagnostic, Therapeutic Insights for Salivary Gland Cancer

Whole-genome sequencing (WGS) of tumor and germline can generate actionable molecular insights that can guide precision medicine efforts in salivary gland cancer (SGC), according to a new study in JCO Precision Oncology.¹

Following tumor biopsies and blood sampling, WGS results of 14 patients with recurrent or metastatic (R/M) SGC revealed the presence of genomic rearrangements or fusions in 12 patients, including MYB fusions in 60% of patients with adenoid cystic carcinoma (AdCC), as well as novel rearrangements (NFIB-QDPR and NFIB-PHIP). Small somatic alterations and germline alterations were observed in all but 1 patient.

Of note, 1 patient harbored a clinically actionable FGFR1-pleomorphic adenoma gene 1 fusion and demonstrated durable responses to the fibroblast growth factor receptor-targeted therapy pemigatinib (Pemazyre) following a daily regimen of 13.5 mg.

“This study adds to existing genomic knowledge in SGC and highlights the role of WGS in SGC research for informing underlying tumor biology and identifying novel targets,” said the authors, Church et al, in the study.¹

Patient Characteristics and Histologic Distribution

Fifteen patients with R/M SGC from a single center in the United Kingdom were initially recruited for the study. One patient failed WGS quality control, resulting in an analytic sample of 14 total patients. All patients had undergone standard-of-care DNA next-generation sequencing and RNA fusion testing panels.

The median age of the group was 56 years (range, 38–76) and more than half (64%) were female. In terms of histologic distribution, the majority of patients had AdCC (n = 10); other subtypes represented in the sample included salivary duct carcinoma ex pleomorphic adenoma (n = 1), clear cell myoepithelial carcinoma (n = 1), epithelial-myoepithelial carcinoma (n = 1), and acinic cell carcinoma (n = 1).

Clinical Value of WGS in a Rare Cancer

SGC is an extremely rare malignancy with over 30 histopathologic subtypes, comprising 0.5% of cancers.¹ The current standard of care for SGC is surgery and radiotherapy; however, approximately 20% of patients with SGC eventually develop metastatic disease with a median overall survival of 15 months, opening opportunities for precision medicine approaches to ameliorate these suboptimal outcomes in advanced disease.

The rarity of SGC has impeded research and development efforts for targeted treatments, as low case numbers make clinical trial recruitment and initiation difficult. Further, its histologic features often overlap across subtypes, complicating diagnosis. As such, this study was motivated by the critical need to build upon this limited evidence base by characterizing molecular profiles and patterns to aid histologic classification and identify targets for treatments.

The study’s findings have potential to be practice-changing, providing a more detailed understanding of this biologically complex cancer and laying the groundwork for future treatment standards.

On the specific clinical utility of WGS, the study authors said, “This study demonstrates that WGS can be performed in clinically relevant timescales, can direct personalized medicine, and aid histopathologic classification in uncertain cases.”

The authors noted that while additional studies are warranted to confirm the utility of WGS, the results highlight the promise of the approach in improving diagnostic precision and facilitating targeted therapy development for these rare tumors.

REFERENCE:

1. Church M, Burghel G, Betts G, et al. Clinical Utility of Whole-Genome Sequencing to Aid Histologic Diagnosis and to Direct Personalized Medicine in Salivary Gland Cancer. JCO PO. 2025;(9). doi:10.1200/po-25-00490