Oncotarget

Research Papers:

Somatic mutations in salivary duct carcinoma and potential therapeutic targets

Timothy K. Khoo, Bing Yu, Joel A. Smith, Angus J. Clarke, Peter P. Luk, Christina I. Selinger, Kate L. Mahon, Spiridoula Kraitsek, Carsten Palme, Michael J. Boyer, Marcel E. Dinger, Mark J. Cowley, Sandra A. O’Toole, Jonathan R. Clark and Ruta Gupta _

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Oncotarget. 2017; 8:75893-75903. https://doi.org/10.18632/oncotarget.18173

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Abstract

Timothy K. Khoo1,*, Bing Yu1,2,*, Joel A. Smith3, Angus J. Clarke1, Peter P. Luk4, Christina I. Selinger4, Kate L. Mahon1,5, Spiridoula Kraitsek2, Carsten Palme1,3, Michael J. Boyer1,5, Marcel E. Dinger6, Mark J. Cowley6, Sandra A. O’Toole1,4, Jonathan R. Clark1,3,7,* and Ruta Gupta1,3,4,*

1Central Clinical School, The University of Sydney, Australia

2Department of Medical Genomics, Royal Prince Alfred Hospital, Sydney, Australia

3The Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse, Sydney, Australia

4Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia

5The Department of Medical Oncology, Chris O’Brien Lifehouse, Sydney, Australia

6Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia

7South West Clinical School, University of New South Wales, Sydney, Australia

*These authors contributed equally to this work

Correspondence to:

Ruta Gupta, email: [email protected]

Keywords: salivary duct carcinoma, somatic mutation analysis, targeted therapies, androgen receptor, HER2

Received: January 10, 2017     Accepted: March 20, 2017     Published: May 25, 2017

ABSTRACT

Background: 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.

Results: 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.

Materials and Methods: 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.

Conclusions: SDCa show multiple somatic mutations, some that are amenable to pharmacologic manipulation and others that confer resistance to treatments currently under investigation. These findings emphasize the need to develop testing and treatment strategies for SDCa.


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