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Updated: Dec 9, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Integrative genomic analysis of salivary duct carcinoma
Youngwook Kim1,2,3, Sanghoon Song4, Miran Lee5
1Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea.
Abstract:
Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally applicable except in very limited cases, and there exists a strong need for the development of treatment against this unique tumor type. To further interrogate genomic features of SDC, we have conducted multi-omic profiling of the SDC to describe the genomic alterations prevalent in this disease. Whole-genome sequencing, whole exome-sequencing and transcriptome sequencing were performed on a discovery cohort of 10 SDC samples. Targeted genomic profiling was performed in additional 32 SDC samples to support the findings obtained from the original discovery cohort. The cancer cohort was characterized by an average mutation burden of 85 somatic exonic mutations per tumor sample. The cohort harbored a mutational signature of BRCA and APOBEC/AID. Several genes, including TP53, RB1, SMAD4, HRAS, APC, PIK3CA and GNAQ were recurrently somatically altered in SDC. A novel fusion gene, generated by genomic rearrangement, MYB-NHSL1, was also noted. Our findings represent a significant layer in the systematic understanding of potentially clinically useful genomic and molecular targets for a subset of recurrent/metastatic SDC.
Insights
Genomic profiling of salivary duct carcinoma (SDC) reveals key alterations and a novel MYB-NHSL1 fusion gene. These findings offer potential therapeutic targets for aggressive SDC, addressing a critical need for effective treatments.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Salivary duct carcinoma (SDC) is an aggressive cancer with limited treatment options for recurrent or metastatic disease.
- Current therapies like chemotherapy and radiation show minimal efficacy.
- There is a significant unmet need for targeted treatments against SDC.
Purpose of the Study:
- To comprehensively analyze the genomic landscape of SDC.
- To identify prevalent genomic alterations and potential therapeutic targets.
- To understand the molecular basis of SDC for improved treatment strategies.
Main Methods:
- Multi-omic profiling including whole-genome, exome, and transcriptome sequencing on a discovery cohort (10 SDCs).
- Targeted genomic profiling on an additional cohort (32 SDCs) to validate findings.
- Analysis of mutation burden, mutational signatures, and gene alterations.
Main Results:
- SDC samples exhibited an average mutation burden of 85 somatic exonic mutations.
- Mutational signatures associated with BRCA and APOBEC/AID were identified.
- Recurrent somatic alterations in TP53, RB1, SMAD4, HRAS, APC, PIK3CA, and GNAQ were observed.
- A novel MYB-NHSL1 fusion gene resulting from genomic rearrangement was discovered.
Conclusions:
- This study provides a detailed genomic characterization of SDC.
- Identified genomic alterations and the MYB-NHSL1 fusion represent potential therapeutic targets.
- Findings contribute to a better understanding of SDC biology and offer avenues for developing novel treatments for recurrent/metastatic SDC.
