Molecular profiling of cancer outliers.

Abstract

e13025 Background: A few patients with metastatic cancer survive exceptionally longer than others under the same treatment. We hypothesized that there is a specific biologic signature in genetic profiles of long-term survivors that plays a key role in sensitivity to systemic treatment. Methods: Twenty-six patients with metastatic cancer treated at Fox Chase cancer center with exceptional response were included in the study. Exceptional response was defined as complete response > 1 year or stable disease/partial response > 2 years at any time during the disease course. Archived tumor specimens of 16 patients were sequenced and analyzed using Ambry Genetics 142 gene panel. In addition, genes expressions in tumor tissues from 23 exceptional responders and 23 matched controls (age, sex and tumor type) were analyzed using two NanoString nCounter PanCancer panels (Pathway and Immune Profiling). Results: See Table. Conclusions: Multiple common mutations of NOTCH2, NF1, FANCD2, PIK3CB and EPHA5 were found in tumors that responded exceptionally well to treatments. Additionally, certain genes were significantly over-expressed or under-expressed in these tumors compared to matched controls. Underlying mechanisms that these genetic alterations foster, leading to susceptibility to treatment and prolonged patient survival, should be further studied. [Table: see text]