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Updated: May 16, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment
Valentina Nardi1, Peter M Sadow, Dejan Juric
1Departments of Pathology and Medicine, Massachusetts General Hospital; Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Purpose:
Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents.
Experimental Design:
We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011. These included the tumors of 8 patients who were tested prospectively. Targeted mutational analysis of 13 clinically relevant cancer genes was conducted using SNaPshot multiplexed genotyping. FISH was conducted to detect HER2 gene amplification. Patient medical records and tumor histopathologic features were retrospectively reviewed.
Results:
Mutually exclusive genetic aberrations were detected in 15 of 27 (56%) tumors, including 2 (7%) mutations in BRAF, 5 (19%) mutations in PIK3CA, and 8 (30%) cases of HER2 gene amplification. To our knowledge, this is the first time that BRAF and PIK3CA mutations have been reported in this tumor type. Prospective clinical testing of 8 patients with SDC identified actionable genetic alterations in 6 tumors and influenced therapeutic decisions for all 6 patients.
Conclusion:
SNaPshot molecular profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad-based genetic profiling to expedite the identification of effective-targeted therapies for patients with rare malignancies.
Insights
Genotyping analysis of salivary duct carcinomas (SDC) revealed novel BRAF and PIK3CA mutations and HER2 amplification. This molecular profiling identified actionable targets, improving treatment strategies for this rare cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Salivary duct carcinomas (SDC) are rare, aggressive salivary gland cancers.
- Current chemotherapy options for SDC have limited efficacy.
- Identifying novel therapeutic targets is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate whether genotyping analysis could detect novel tumor-specific mutations in SDC.
- To identify potential targeted agents for SDC patient treatment.
- To expand therapeutic options for patients with this rare malignancy.
Main Methods:
- Genotyping analysis of 27 SDC archival specimens using SNaPshot multiplexed genotyping.
- Targeted mutational analysis of 13 clinically relevant cancer genes.
- FISH analysis for HER2 gene amplification.
- Retrospective review of patient medical records and tumor histopathology.
Main Results:
- Mutually exclusive genetic aberrations were detected in 56% of SDC tumors.
- Mutations in BRAF (7%) and PIK3CA (19%) were identified for the first time in SDC.
- HER2 gene amplification was detected in 30% of cases.
- Actionable genetic alterations were found in 6 of 8 prospectively tested patients, influencing therapeutic decisions.
Conclusions:
- SNaPshot molecular profiling identified novel genetic changes in SDCs.
- Expanded therapeutic options for SDC patients through targeted therapies.
- Broad-based genetic profiling is essential for identifying effective treatments for rare malignancies.
