title: Detection of the G17V RHOA mutation in angioimmunoblastic T-cell lymphoma and related lymphomas using quantitative allele-specific PCR.
abstract: Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) are subtypes of T-cell lymphoma. Due to low tumor cell content and substantial reactive cell infiltration, these lymphomas are sometimes mistaken for other types of lymphomas or even non-neoplastic diseases. In addition, a significant proportion of PTCL-NOS cases reportedly exhibit features of AITL (AITL-like PTCL-NOS). Thus disagreement is common in distinguishing between AITL and PTCL-NOS. Using whole-exome and subsequent targeted sequencing, we recently identified G17V RHOA mutations in 60-70% of AITL and AITL-like PTCL-NOS cases but not in other hematologic cancers, including other T-cell malignancies. Here, we establish a sensitive detection method for the G17V RHOA mutation using a quantitative allele-specific polymerase chain reaction (qAS-PCR) assay. Mutated allele frequencies deduced from this approach were highly correlated with those determined by deep sequencing. This method could serve as a novel diagnostic tool for 60-70% of AITL and AITL-like PTCL-NOS.
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakamoto-Matsubara
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Sakata-Yanagimoto
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Terukazu
authors.initials: T
authors.lastname: Enami
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Division for Health Service Promotion, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yanagimoto
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shiozawa
authors.affiliation: Department of Clinical Laboratory, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nanmoku
authors.affiliation: Department of Pathology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Kaishi
authors.initials: K
authors.lastname: Satomi
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Muto
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Obara
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan; Life Science Center, Tsukuba Advanced Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kurita
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Hematology, Toranomon Hospital, Minato-ku, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Minato-ku, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Izutsu
authors.affiliation: Department of Pathology, Toranomon Hospital, Minato-ku, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ota
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanada
authors.affiliation: Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan; Department of Hematology, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan; Department of Hematology, Mito Medical Center, National Hospital Organization, Ibaraki-machi, Ibaraki, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Komeno
authors.affiliation: Department of Hematology, Tsukuba Memorial Hospital, Tsukuba, Ibaraki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Hematology, JA Toride Medical Center, Toride, Ibaraki, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Issay
authors.initials: I
authors.lastname: Kitabayashi
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Hematology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan; Life Science Center, Tsukuba Advanced Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis / Q000379:methods*; D059472:Exome; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016399:Lymphoma, T-Cell / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction / Q000379:methods*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein