Abstract 2008: Genomic medicine using NexGen sequencing to personalized treatment of metastatic adenoid cystic carcinoma (ADCC).
Authors: Huang Chao H. , Hoang Yen , Minn Kay , Godwin Andrew , Chien Jeremy 
Published: August 2014

Abstract
Background:
ADCC is a form of cancer usually originating from saliva gland. The standard treatment is surgical resection followed by adjuvant radiation if indicated. Cases of metastatic disease can behave indolently but ultimately can be fatal and there is no effective therapy. We present the results of NexGen sequencing of a 41yo caucasian female diagnosed with ADCC in 2003 who subsequently developed recurrence in 2005 and pulmonary metastases in 2006. She was treated with multiple agents including radiation. She had further progression with increase dyspnea in 2012. Commercial profiling by Caris Biosciences found expression of VEGFR, PDGFRA and PDGFRB. She was treated with Sorafenib, an oral multikinase inhibitor of the VEGFR, PDGFR, and BRAF without improvement, and she developed further dyspnea requiring oxygen. We performed NexGen sequencing of a biopsied metastatic lesion to identify somatic mutations and to determine if any targeted agent would be of further benefit. Results: NextGen sequencing was performed on DNA extracted from formalin-fixed tumor biopsy sample. Blood DNA served as control. Using Illumina TruSeq Exome Enrichment kit, 100 bp paired-end sequencing was performed on the tumor and normal exomes. Resulting sequences were mapped to the Human Reference Genome (hg19) using two bioinformatics workflows: CLC Genomics Workbench and BWA/GATK. Single nucleotide variants (SNVs) and small insertions/deletions (INDELs) were separately characterized for normal and tumor exomes. Finally, germline variants (SNVs and INDELs) were subtracted to identify putative somatic mutations in tumor exome. Concensus somatic mutations were obtained from CLC and BWA/GATK workflows. A total of 569 non-synonymous mutations and 35 stopgain mutations were observed in the tumor exome. Mutations in BRCA2, IGF1R, KDR, MTOR, TP63, XPC, RAD17, MLH1, and PTEN were observed in the tumor exome. Mutations in the components of kinase-mediated signaling (IGF1R, KDR, MTOR, PTEN) are potential targets of kinase and mTOR inhibitors whereas mutations in the DNA repair pathways (TP63, XPC, RAD17, MLH1) may be targeted with DNA alkylating agents. The result indicates that patient's tumor harbor several mutations that can be targeted by available cancer drugs. Conclusions: We found several mutated molecular pathways that can be targeted with available agents using exome sequencing. Improvement in outcome could validate the role of exome sequencing in treatment selection of advanced cancers without standard therapy.
Citation Format: Chao H. Huang, Yen Hoang, Kay Minn, Andrew Godwin, Jeremy Chien. Genomic medicine using NexGen sequencing to personalized treatment of metastatic adenoid cystic carcinoma (ADCC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2008. doi:10.1158/1538-7445.AM2013-2008