Abstract 4280: Integrative analyses of multi-omics sequencing data to guide treatment decisions in a patient with double malignancy

Abstract

Abstract Multiple primary malignancies are becoming common. The number of second or higher-order cancers is burgeoning and accounted for about 16% of incident cancers. Double malignancy cases pose the problem of finding the best treatment for the patient. Next generation sequencing (NGS) was used in this study to characterize the genetic and genomic composition in a patient with multiple cancer syndromes. A lung adenocarcinoma brain metastasis sample (FFPE) naïve to any tumor therapy, and relapsed primary lung adenocarcinoma and ovarian serous carcinoma tumor biopsies (fresh frozen) were procured from a 51-year old Chinese female never-smoker. The primary lung and ovarian cancer samples were post to the treatments with both first line and EGFR-TKI targeted therapy. Multiple NGS approaches were conducted on the patient biopsies, including DNA whole genome/exome sequencing, RNA sequencing, and microRNA sequencing. Integrative analyses of the comprehensive NGS data indicated EGFR exon 19 deletions in-frame, which encode part of the kinase domain presented in both primary lung cancer and its brain metastases. EGFR T790M mutation which accounts for the resistance of lung tumor to the EGFR-TKI therapy was identified in the relapsed lung sample but not in the brain malignancy. These results were well aligned with the clinical response to EGFR-TKI treatment in the patient. Furthermore, we uncovered frequent occurrences of somatic copy number variations in both lung and ovarian tumors. A somatic non-sense mutation (COSMIC ID: 307331) in TP53 was uniquely identified in the ovarian tumor biopsy, suggesting a different mechanism driving tumorigenesis than that in the lung. Besides, we also identified a heterozygous insertion in DUSP16 and a stop code gained mutation in MAP3K15 in the patient's germline DNA, a potential predisposition of multiple cancer syndromes and early onset of tumor in this patient. Finally, structural variation and gene fusion, gene interaction, pathway analysis of the affected genes were integrated and evaluated. Overall, NGS approaches shed insights into the molecular phenotypes of tumors and thus have the potential to provide the physician key scientific rationale to design targeted therapeutic approaches in the treatment course. Citation Format: Wei Zhu, Jiaqi Huang, Brandon W. Higgs, Philip Brohawn, Shujun Dai, Laura Richman, Bahija Jallal, Liyan Jiang, Yihong Yao. Integrative analyses of multi-omics sequencing data to guide treatment decisions in a patient with double malignancy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4280. doi:10.1158/1538-7445.AM2014-4280