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المؤلفGargano, Stacey M
المؤلفSenarathne, Wijendra
المؤلفFeldman, Rebecca
المؤلفFlorento, Elena
المؤلفStafford, Phillip
المؤلفSwensen, Jeffrey
المؤلفVranic, Semir
المؤلفGatalica, Zoran
تاريخ الإتاحة2019-10-15T11:01:04Z
تاريخ النشر2019-10-14
اسم المنشورCancer Medicine
المعرّفhttp://dx.doi.org/10.1002/cam4.2602
الاقتباسGargano, SM, Senarathne, W, Feldman, R, et al. Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling. Cancer Med. 2019; 00: 1– 8. https://doi.org/10.1002/cam4.2602
معرّف المصادر الموحدhttp://hdl.handle.net/10576/12121
الملخصSalivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized by HER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant-7 (AR-V7) in some SDC cases could result in resistance to anti-androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next-generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations were found in all but 1 case and affected TP53 (n = 19), HRAS (n = 7), PIK3CA, ERBB2 (HER2), and NF1 (n = 5 each); KMT2C (MLL3) and PTEN (n = 3 each); BRAF (p.V600E), KDM5C and NOTCH1 (n = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR-V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was expressed in 11 of 28 cases. The majority of SDC cases had no biomarkers predictive of immunotherapy response: 5 cases exhibited low (1%-8%) programmed death ligand 1 (PD-L1) expression in tumor cells, 2 cases exhibited elevated TMB, and no samples exhibited microsatellite instability. Notably, the pre-treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti-androgen therapy, showed AR expression and no AR splice variants. We conclude that comprehensive molecular profiling of SDCs can guide the selection of patients for targeted therapies involving AR, HER2, PD-L1, mitogen-activated protein kinase, and PIK3CA pathways.
اللغةen
الناشرWiley Open Access
الموضوعbiomarkers
head and neck cancer
molecular genetics
next generation sequencing
salivary glands
العنوانNovel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling.
النوعArticle
الصفحات1– 8
ESSN2045-7634
dc.accessType Open Access


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