title: Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms.
abstract: Cohesin is a multimeric protein complex that is involved in the cohesion of sister chromatids, post-replicative DNA repair and transcriptional regulation. Here we report recurrent mutations and deletions involving multiple components of the cohesin complex, including STAG2, RAD21, SMC1A and SMC3, in different myeloid neoplasms. These mutations and deletions were mostly mutually exclusive and occurred in 12.1% (19/157) of acute myeloid leukemia, 8.0% (18/224) of myelodysplastic syndromes, 10.2% (9/88) of chronic myelomonocytic leukemia, 6.3% (4/64) of chronic myelogenous leukemia and 1.3% (1/77) of classical myeloproliferative neoplasms. Cohesin-mutated leukemic cells showed reduced amounts of chromatin-bound cohesin components, suggesting a substantial loss of cohesin binding sites on chromatin. The growth of leukemic cell lines harboring a mutation in RAD21 (Kasumi-1 cells) or having severely reduced expression of RAD21 and STAG2 (MOLM-13 cells) was suppressed by forced expression of wild-type RAD21 and wild-type RAD21 and STAG2, respectively. These findings suggest a role for compromised cohesin functions in myeloid leukemogenesis.
authors: Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Ayana
authors: A
authors: Kon
authors: Lee-Yung
authors: LY
authors: Shih
authors: Masashi
authors: M
authors: Minamino
authors: Masashi
authors: M
authors: Sanada
authors: Yuichi
authors: Y
authors: Shiraishi
authors: Yasunobu
authors: Y
authors: Nagata
authors: Kenichi
authors: K
authors: Yoshida
authors: Yusuke
authors: Y
authors: Okuno
authors: Masashige
authors: M
authors: Bando
authors: Ryuichiro
authors: R
authors: Nakato
authors: Shumpei
authors: S
authors: Ishikawa
authors: Aiko
authors: A
authors: Sato-Otsubo
authors: Genta
authors: G
authors: Nagae
authors: Aiko
authors: A
authors: Nishimoto
authors: Claudia
authors: C
authors: Haferlach
authors: Daniel
authors: D
authors: Nowak
authors: Yusuke
authors: Y
authors: Sato
authors: Tamara
authors: T
authors: Alpermann
authors: Masao
authors: M
authors: Nagasaki
authors: Teppei
authors: T
authors: Shimamura
authors: Hiroko
authors: H
authors: Tanaka
authors: Kenichi
authors: K
authors: Chiba
authors: Ryo
authors: R
authors: Yamamoto
authors: Tomoyuki
authors: T
authors: Yamaguchi
authors: Makoto
authors: M
authors: Otsu
authors: Naoshi
authors: N
authors: Obara
authors: Mamiko
authors: M
authors: Sakata-Yanagimoto
authors: Tsuyoshi
authors: T
authors: Nakamaki
authors: Ken
authors: K
authors: Ishiyama
authors: Florian
authors: F
authors: Nolte
authors: Wolf-Karsten
authors: WK
authors: Hofmann
authors: Shuichi
authors: S
authors: Miyawaki
authors: Shigeru
authors: S
authors: Chiba
authors: Hiraku
authors: H
authors: Mori
authors: Hiromitsu
authors: H
authors: Nakauchi
authors: H Phillip
authors: HP
authors: Koeffler
authors: Hiroyuki
authors: H
authors: Aburatani
authors: Torsten
authors: T
authors: Haferlach
authors: Katsuhiko
authors: K
authors: Shirahige
authors: Satoru
authors: S
authors: Miyano
authors: Seishi
authors: S
authors: Ogawa
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins
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