| Title: | Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia |
| Authors: | Hashiguchi, Junichi Browse this author |
| Onozawa, Masahiro Browse this author →KAKEN DB |
| Oguri, Satoshi Browse this author |
| Fujisawa, Shinichi Browse this author |
| Tsuji, Masahisa Browse this author |
| Okada, Kohei Browse this author |
| Nakagawa, Masao Browse this author |
| Hashimoto, Daigo Browse this author →KAKEN DB |
| Kahata, Kaoru Browse this author |
| Kondo, Takeshi Browse this author →KAKEN DB |
| Shimizu, Chikara Browse this author →KAKEN DB |
| Teshima, Takanori Browse this author →KAKEN DB |
| Keywords: | FISH |
| illegitimate V(D)J rearrangement |
| IKZF1 |
| ikaros |
| RAG1/2-mediated rearrangement |
| Issue Date: | Jul-2018 |
| Publisher: | Elsevier |
| Journal Title: | The Journal of Molecular Diagnostics |
| Volume: | 20 |
| Issue: | 4 |
| Start Page: | 446 |
| End Page: | 454 |
| Publisher DOI: | 10.1016/j.jmoldx.2018.02.005 |
| PMID: | 29957452 |
| Abstract: | Intragenic deletion of IKZF1 is a recurrent genomic alteration in acute lymphoblastic leukemia. The deletions are mediated by illegitimate variable(diversity)joining recombination via cryptic recombination signal sequences (RSSs). We developed a fluorescence in situ hybridization (FISH) probe set that can detect any type of IKZF1 deletion, including the commonly deleted exon 4 to 7 region. The probe set consists of a designed probe for the commonly deleted region (Cy3; red) and a bacterial artificial chromosomes clone probe for detecting the 3' flanking region (Spectrum Green). Intact IKZF1 showed a fusion signal, and the deleted allele showed loss of the red signal (0R1G1F). The FISH probes worked correctly for human leukemic cell lines and clinical samples. One case showed an atypical break-apart signal (1R1G1F). Inverse PCR of the case revealed rearrangement of the excised IKZF1 fragment into a legitimate RSS site at Ig κ on chromosome 2, suggesting a pathogenic role of this recombination-activating gene 1/2-mediated event. In this study, we established FISH probe detecting IKZF1 deletion in a quick, quantitative, and cost-effective manner, and the results provided a novel insight into B-cell receptor editing by rearrangement of a cryptic RSS-mediated genomic fragment in acute lymphoblastic leukemia pathology. |
| Rights: | ©2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/74830 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
