Identification and characterization of a novel adenomatous polyposis coli mutation in adult pancreatoblastoma

// Shigeo Yamaguchi 1, * , Tomoaki Fujii 2, * , Yuki Izumi 3, * , Yuki Fukumura 4 , Min Han 1 , Hideki Yamaguchi 5 , Tomomi Akita 3, 6 , Chikamasa Yamashita 3, 6 , Shunsuke Kato 1, 7 and Takao Sekiya 2 1 Department of Clinical Oncology, Juntendo University Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan 2 Department of Cancer Genome Research, Sasaki Institute, Sasaki Foundation, Kandasurugadai, Chiyoda-ku, Tokyo, Japan 3 Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda, Chiba, Japan 4 Department of Human Pathology, Faculty of Medicine, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan 5 Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Kandasurugadai, Chiyoda-ku, Tokyo, Japan 6 Fusion of Regenerative Medicine with DDS, Research Institute for Science and Technology, Tokyo University of Science, Yamazaki, Noda, Chiba, Japan 7 Division of Translational Genomics for Intractable Diseases, Intractable Diseases Research Center, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan * These authors contributed equally to this work Correspondence to: Shunsuke Kato, email: katoshun@juntendo.ac.jp Keywords: next generation sequencing; variant of uncertain significance; pancreatoblastoma; adenomatous polyposis coli; Wnt/β-catenin signaling Received: September 14, 2017 Accepted: January 02, 2018 Published: January 06, 2018 ABSTRACT During next generation sequencing (NGS) analysis, many missense mutations were found in a well-known oncogene, many of which were variant of uncertain significance mutations. We recently treated an adult patient with pancreatoblastoma by chemotherapy. Using an NGS cancer panel, we found a previously unreported missense mutation in the 1835 codon of the adenomatous polyposis coli ( APC ) gene. We also found a heterogeneous mutation in the 1835 codon of the APC gene in the patient’s germline by Sanger sequencing. Although this patient did not have a history of familial adenomatous polyposis, functional analysis suggested the R1835G mutant APC showed attenuated repression of Wnt/β-catenin signaling activity. This is the first report showing a novel APC missense mutation involved in the onset of adult pancreatoblastoma.