Mutant allele-specific imbalance in patients with metastatic colorectal cancer.

Abstract

706 Background: Patients with colorectal cancer(CRC) harboring RAS mutations do not respond to antiepidermal growth factor receptor (anti-EGFR) therapy. Next generation sequencing (NGS) identifies and quantifies mutant and wild type alleles as seen on the sequencing electropherograms. RAS mutant allele-specific imbalance (MASI) occurs when the mutant allele peak is higher than the wild type one. The aims of this study were to verify the rate and tissue distribution of RAS MASI as well as its clinical relevance. Methods: Results of NGS study of patients with metastatic colorectal cancer were collected retrospectively. The clinical charts of patients with RAS mutations were reviewed by the investigators who were blinded to the MASI results. Results: Between August 2014 and Jan 2016, 26 out of 52 (50%)patients tested, were found to harbor RAS mutations. Among them, 11 patients were detected with KRAS MASI(42.3%) Table 1 shows the different characteristics. 6 out of 11 patients presented with synchronous metastatic disease. This correlated with a statistically significant difference in the mean disease free survival that was 9 months in the KRAS MASI group compared with 27.5 months in the non MASI group. A few patients had more than one mutation. ie KRAS Ex2- G12D, 62.3%, PKI3CA Ex9-E545K, 24.6%, Ex20-H1047Y, 0.6% in the MASI group and KRAS Ex2-G12C+G12V - 10.85%, KRAS Ex4-A146T - 10.3%, NRAS gene Ex2-G12D - 1.1%, in non MASI group. Patients in the MASI group had a different clinical profile. (See Table 1) The overall survival of patients was calculated from diagnosis of metastatic disease, till death, 24 months-this was not significantly nor statistically different amongst groups. Conclusions: With the caveat of a small study and a retrospective analysis we showed that patients with MASI have worse characteristics that were translated to a significant shorter disease free survival. OS was not different amongst the groups. [Table: see text]