Somatic mutations in salivary duct carcinoma and potential therapeutic targets

Oncotarget
Timothy K KhooRuta Gupta

Abstract

Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p.H1047R: Everolimus), ERBB2 (p.V842I: Lapatinib), HRAS (p.Q61R: Selumetinib) and KIT (p.T670I: Sorafenib). Furthermore, alterations in PTEN, PIK3CA and HRAS that alter response to androgen deprivation therapy and HER2 inhibition were also seen. Somatic mutation analysis was performed on DNA extracted from 15 archival cases of SDCa using the targeted Illumina TruSeq Amplicon Cancer Panel. Potential targetable genetic alterations were identified using extensive literature and international somatic mutation database (COSMIC, KEGG) search. Immunohistochemistry for androgen receptor and immunohistochemistry and fluorescent in situ hybridization for HER2 were also performed. SDCa show multiple somatic mutations, some that are amenable to pharmacologic manipulation and others th...Continue Reading

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Citations

Jan 27, 2018·Current Opinion in Otolaryngology & Head and Neck Surgery·Emmanuel D'heygereVincent Vander Poorten
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Jul 13, 2021·Frontiers in Oncology·Kristian EgebjergMorten Mau-Sørensen

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Methods Mentioned

BETA
surgical resection
dissection
exome sequencing

Software Mentioned

COSMIC
Illumina Somatic Variant Caller
PolyPhen
Illumina variant studio
Isis
SIFT
FATHMM

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