Detection of novel and potentially actionable anaplastic lymphoma kinase (ALK) rearrangement in colorectal adenocarcinoma by immunohistochemistry screening

摘要: // Jeeyun Lee 1, * , Hee Cheol Kim 2, Jung Yong Hong 3, Kai Wang 4 Sun Young 1 Jiryeon Jang Seung Tae Joon Oh Park Ho Yeong Lim Won Ki Kang Suk Jiyun Woo 2 Yoon Ah Wook Huh Seong Hyeon Yun In-Gu Do 5 Seok Hyung Sohail Balasubramanian Philip J. Stephens Jeffrey S. Ross 4, 6 Gang Gary Li 7 Zachary Hornby Siraj M. Ali Vincent A. Miller Kyoung-Mee 5, 8 Sai-Hong Ignatius Ou 9 Department of Medicine, Division Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School Seoul, Republic Korea Surgery, 3 Internal Chung-Ang College Dongjak-Gu, Foundation Medicine Inc, Cambridge, Massachusetts, USA Pathology and Translational Genomics, Laboratory Albany College, Albany, New York, Ignyta San Diego, California, Innovative Cancer Institute, Chao Family Comprehensive California Irvine Orange, These authors have contributed equally to this work Correspondence to: Ou, e-mail: Ignatius.ou@uci.edu Kim, kkmkys@skku.edu Keywords: colorectal carcinoma, anaplastic lymphoma kinase (ALK) rearrangement, immunohistochemistry, next generation sequencing Received: April 02, 2015      Accepted: June 19, Published: July 01, 2015 ABSTRACT Purpose: Anaplastic rearrangement has been detected in carcinoma (CRC) using advanced molecular diagnostics tests including exon scanning, fluorescence situ hybridization (FISH), (NGS). We investigated if immunohistochemistry (IHC) can be used detect ALK gastrointestinal malignancies. Experimental designs: Tissue microarrays (TMAs) from consecutive gastric (GC) CRC patients who underwent surgical resection at were screened by IHC monoclonal antibody 5A4. positive cases confirmed FISH, nCounter assays, NGS-based comprehensive genomic profiling (CGP). was further applied enrolled a pathway-directed therapeutic trial. Results: Four hundred thirty-two GC 172 IHC. No sample positive. One (0.6%) (3+) that FISH novel CAD-ALK (C35; A20) fusion variant resulted paracentric inversion event inv(2)(p22–21p23) identified CGP. out 50 trial found harbor the EML4-ALK (E21, Growth tumor cell line derived patient inhibited inhibitors crizotinib entrectinib. Conclusions: is viable screening strategy for identifying CRC. potential actionable driver mutation based on survival inhibition tumor-derived potent inhibitors.