Abstract 256: Detection of METexon 14 skipping and fusions in non-small cell lung cancer by comprehensive genomic profiling using a dual targeted DNA/RNA panel
Authors: Kage Hidenori , Kohsaka Shinji , Tatsuno Kenji , Shinozaki-Ushiku Aya , Isago Hideaki , Watanabe Kousuke , Kato Motohiro , Ushiku Tetsuo , Miyagawa Kiyoshi , Nagase Takahide , Nakajima Jun , Aburatani Hiroyuki , Mano Hiroyuki , Oda Katsutoshi 
Published: April 2023

Abstract
Introduction: Comprehensive cancer genomic profiling tests have been implemented in the clinic to guide patients and physicians to decide optimal treatments. Most tests analyze genomic DNA to detect genomic alterations in a few hundred genes. RNA panels have advantages over DNA panels when detecting fusion and exon skipping events.
Methods: Between April 2017 and March 2022, non-small cell lung cancer samples were analyzed by Todai OncoPanel (TOP), a dual targeted DNA/RNA panel with matched tumor/normal pair analysis. Informed consent was obtained from all patients. Publicly available genomic data from approved panels in Japan, all of which are DNA-only panels, was downloaded from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database on 2022/11/3.
Results: Sixty-one samples were analyzed. The median age of the patients was 62, and 35 were men. The histology of the samples included 52 adenocarcinoma and 9 squamous cell carcinoma. Of the 52 adenocarcinoma samples, pathogenic or likely pathogenic mutations were detected in 46 (88%), and 40 samples (77%) harbored potentially druggable targets. With the DNA panel, 23 (44%) TP53 loss-of-function mutations, 17 (33%) EGFR activating mutations, 6 (12%) ERBB2 activating mutations, 5 (10%) KRAS activating mutations, 5 (10%) RB1 loss-of-function mutations, 3 (6%) BRAF activating mutations, and 3 (6%) MET exon 14 splice site mutation were detected. Meanwhile, with the RNA panel, three MET exon 14 skipping and 15 fusion genes in 16 patients (16/61 = 26%) were detected, all in adenocarcinoma. Specifically, EML4-ALK, KIF5B-RET, and CD47-MET were detected from one sample each, and 12 others were all novel fusions with unknown pathogenicity. Overall, 5 out of 61 (8.1%) non-small cell lung cancer samples harbored MET exon 14 skipping or fusion. Using the C-CAT database, 37 MET exon 14 splice site mutations and 2 rearrangements were found in 1,514 non-small cell lung cancer samples (2.6%) from the C-CAT database (p = 0.009). One BRCA1 and one BRCA2 pathogenic germline variants were detected from the TOP germline panel.
Conclusion: Analysis of non-small cell lung cancer using TOP led to detection of a high percentage of druggable targets. TOP RNA panel may detect MET exon 14 skipping and fusions at higher sensitivity.
Citation Format: Hidenori Kage, Shinji Kohsaka, Kenji Tatsuno, Aya Shinozaki-Ushiku, Hideaki Isago, Kousuke Watanabe, Motohiro Kato, Tetsuo Ushiku, Kiyoshi Miyagawa, Takahide Nagase, Jun Nakajima, Hiroyuki Aburatani, Hiroyuki Mano, Katsutoshi Oda. Detection of METexon 14 skipping and fusions in non-small cell lung cancer by comprehensive genomic profiling using a dual targeted DNA/RNA panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 256.