Oncotarget

Research Papers:

Genomic landscape of salivary gland tumors

Shumei Kato _, Sheryl K. Elkin, Maria Schwaederle, Brett N. Tomson, Teresa Helsten, Jennifer L. Carter and Razelle Kurzrock

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:25631-25645. https://doi.org/10.18632/oncotarget.4554

Metrics: PDF 2399 views  |   HTML 2976 views  |   ?  


Abstract

Shumei Kato1, Sheryl K. Elkin2, Maria Schwaederle3, Brett N. Tomson2, Teresa Helsten3, Jennifer L. Carter2, Razelle Kurzrock3

1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2N-of-One, Inc., Lexington, MA, USA

3Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego, Moores Cancer Center, La Jolla, CA, USA

Correspondence to:

Shumei Kato, e-mail: [email protected]

Keywords: salivary gland tumor, next-generation sequencing, genomic landscape, personalized therapy, targeted therapy

Received: April 25, 2015     Accepted: July 15, 2015     Published: July 27, 2015

ABSTRACT

Effective treatment options for advanced salivary gland tumors are lacking. To better understand these tumors, we report their genomic landscape. We studied the molecular aberrations in 117 patients with salivary gland tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One, Inc. (Lexington, MA). There were 354 total aberrations, with 240 distinct aberrations identified in this patient population. Only 10 individuals (8.5%) had a molecular portfolio that was identical to any other patient (with four different portfolios amongst the ten patients).

The most common abnormalities involved the TP53 gene (36/117 [30.8% of patients]), cyclin pathway (CCND1, CDK4/6 or CDKN2A/B) (31/117 [26.5%]) and PI3K pathway (PIK3CA, PIK3R1, PTEN or AKT1/3) (28/117 [23.9%]). In multivariate analysis, statistically significant co-existing aberrations were observed as follows: TP53 and ERBB2 (p = 0.01), cyclin pathway and MDM2 (p = 0.03), and PI3K pathway and HRAS (p = 0.0001). We were able to identify possible cognate targeted therapies in most of the patients (107/117 [91.5%]), including FDA-approved drugs in 80/117 [68.4%]. In conclusion, salivary gland tumors were characterized by multiple distinct aberrations that mostly differed from patient to patient. Significant associations between aberrations in TP53 and ERBB2, the cyclin pathway and MDM2, and HRAS and the PI3K pathway were identified. Most patients had actionable alterations. These results provide a framework for tailored combinations of matched therapies.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 4554