Frequent mutations of genes encoding vacuolar H+‐ATPase components in granular cell tumors

• DOI: 10.1002/gcc.22727
• Publication Date: 2018-12-31T23:01:45Z
• Authors: Masaya Sekimizu; Akihiko Yoshida; Sachiyo Mitani; Naofumi Asano; Makoto Hirata; Takashi Kubo; Fumito Yamazaki; Hiromi Sakamoto; Mamoru Kato; Naohiro Makise; Taisuke Mori; Naoya Yamazaki; Shigeki Sekine; Ichiro Oda; Shun‐ichi Watanabe; Hiroaki Hiraga; Tsukasa Yonemoto; Teruya Kawamoto; Norifumi Naka; Yuki Funauchi; Yoshihiro Nishida; Kanya Honoki; Hirotaka Kawano; Hiroyuki Tsuchiya; Toshiyuki Kunisada; Koichi Matsuda; Katsunori Inagaki; Akira Kawai; Hitoshi Ichikawa
• Keywords: 0301 basic medicine; Vacuolar Proton-Translocating ATPases; 03 medical and health sciences; Mutation Rate; Granular Cell Tumor; Humans; Receptors, Cell Surface

Abstract Granular cell tumors (GCTs) are rare mesenchymal that exhibit a characteristic morphology and finely granular cytoplasm. The genetic alterations responsible for GCT tumorigenesis had been unknown until recently, when loss‐of‐function mutations of ATP6AP1 ATP6AP2 were described. Thus, we performed whole‐exome sequencing, RNA targeted sequencing 51 samples. From these genomic analyses, identified in genes encoding vacuolar H + ‐ATPase (V‐ATPase) components, including , 33 (65%) GCTs. found 23 (45%) 2 (4%) samples, respectively, all truncating or splice site mutations. In addition, seven other V‐ATPase components also mutated, three ATP6V0C occurred on the same amino acid (isoleucine 136). These component gene mutually exclusive, with one exception. results suggest function is impaired GCTs not only by but through subunits. Our findings provide additional support hypothesis dysfunction promotes tumorigenesis.