title: Genomic landscape of salivary gland tumors.
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.
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shumei
authors.initials: S
authors.lastname: Kato
authors.affiliation: N-of-One, Inc., Lexington, MA, USA.
authors.forename: Sheryl K
authors.initials: SK
authors.lastname: Elkin
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego, Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Schwaederle
authors.affiliation: N-of-One, Inc., Lexington, MA, USA.
authors.forename: Brett N
authors.initials: BN
authors.lastname: Tomson
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego, Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Helsten
authors.affiliation: N-of-One, Inc., Lexington, MA, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Carter
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego, Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016015:Logistic Models; D015999:Multivariate Analysis; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: genomic landscape; next-generation sequencing; personalized therapy; salivary gland tumor; targeted therapy