Clinical Utility of Whole-Genome Sequencing to Aid Histologic Diagnosis and to Direct Personalized Medicine in Salivary Gland Cancer

RESEARCH SPOTLIGHT: Clinical Utility of Whole-Genome Sequencing to Aid Histologic Diagnosis and to Direct Personalized Medicine in Salivary Gland Cancer

Abstract

PURPOSE

Salivary gland cancers (SGCs) are rare and comprise multiple histologic entities. In the recurrent or metastatic (R/M) setting, there is limited evidence for effective systemic anticancer treatment for most subtypes, affecting prognosis and quality of life. Molecular analysis of SGCs holds promise to more accurately classify SGC subtypes and to determine novel therapeutic targets.

MATERIALS AND METHODS

Fifteen patients with R/M SGC underwent tumor biopsy and blood sampling to perform whole-genome sequencing (WGS) of tumor and germline as part of their standard-of-care management. Small somatic mutations, structural alterations, copy number variation, and mutational signatures were processed using WGS pipelines alongside germline testing. Alterations were correlated to clinical features and fed back to clinical team to inform treatment decisions.

RESULTS

WGS quality control was acceptable in 14 of 15 patients (adenoid cystic carcinoma [AdCC, n = 10], 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]). Genomic rearrangements/fusions were present in 12 of 14. Rearrangements involving MYB and or NFIB were identified in 8 of 10 patients with AdCC. One patient harbored a clinically actionable FGFR1-pleomorphic adenoma gene 1 fusion and responded to fibroblast
growth factor receptor–targeted therapy, in addition to enabling histologic reclassification. Other fusions included EWSR1-ATF1 and CRTC1-MAML2, which also aided definitive histologic classification. Small somatic alterations were identified in all but one patient. There were no pathogenic germline mutations.

CONCLUSION

WGS in SGC is achievable in clinically relevant timeframes, providing genomic information for deeper understanding of disease pathophysiology, to clarify histologic subtype and can identify actionable genomic targets which may not be found through routine sequencing technologies. Further use of WGS has the potential to improve care for patients with SGC.

Read the full paper here: JCO Precis Oncol. 2025 Oct;9:e2500490. (doi: 10.1200/PO-25-00490)

Understand the Science: Watch the Video
For a clear, plain-English explanation of whole genome sequencing and how this research impacts SGC patients, please watch Dr. Matt Church's video of his presentation at one of SGC UK's patient gatherings: Watch Here: Whole Genome Sequencing With Dr Matt Church For Salivary Gland Cancer UK | March 2024 Gathering

There is more information about genomics here: Gene profiling or tumour profiling or genomic testing - Salivary Gland Cancer UK

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Last updated January 2026