SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo.
SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo.
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DOI：
10.1002/ajmg.a.35532
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发表时间：
2012-09
影响因子：
2
通讯作者：
Boerkoel, Cornelius F.
中科院分区：
文献类型：
--
作者：
Baradaran-Heravi, Alireza;Raams, Anja;Lubieniecka, Joanna;Cho, Kyoung Sang;DeHaai, Kristi A.;Basiratnia, Mitra;Mari, Pierre-Olivier;Xue, Yutong;Rauth, Michael;Olney, Ann Haskins;Shago, Mary;Choi, Kunho;Weksberg, Rosanna A.;Nowaczyk, Malgorzata J. M.;Wang, Weidong;Jaspers, Nicolaas G. J.;Boerkoel, Cornelius F.
Schimke 免疫性骨发育不良 (SIOD) 是一种多系统疾病，具有明显的骨骼、肾脏、免疫和外胚层异常。它是由 SMARCAL1（SWI/SNF 相关、基质相关、肌动蛋白依赖性染色质调节因子，a 类亚家族 1）突变引起的，该蛋白编码 DNA 应激反应蛋白。为了确定该功能与 SIOD 表型的关系，我们分析了 SIOD 中的癌症患病率，并评估了核苷酸切除修复 (NER) 和非同源末端连接 (NHEJ) 的缺陷是否分别解释了 SIOD 的外胚层和免疫学特征。最后，我们确定 Smarcal1del/del 小鼠是否对伊立替康 (CPT-11)、依托泊苷和羟基脲 (HU) 过敏，以及暴露于这些药物是否会诱发 SIOD 特征。在 71 名 SIOD 患者中，3 名患有非霍奇金淋巴瘤 (NHL)，1 名患有骨肉瘤。我们没有发现 NER 或 NHEJ 有缺陷的证据；然而，Smarcal1 缺陷小鼠对几种基因毒性剂过敏。此外，CPT-11、依托泊苷和 HU 导致生长板软骨细胞生长减少和损失。这些数据确定了 SIOD 中 NHL 患病率的增加，并证实了体内对 DNA 损伤剂的过敏，为 SIOD 患者的管理提供了指导。
Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder with prominent skeletal, renal, immunological, and ectodermal abnormalities. It is caused by mutations of SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA stress response protein. To determine the relationship of this function to the SIOD phenotype, we profiled the cancer prevalence in SIOD and assessed if defects of nucleotide excision repair (NER) and of nonhomologous end joining (NHEJ), respectively, explained the ectodermal and immunological features of SIOD. Finally, we determined if Smarcal1del/del mice had hypersensitivity to irinotecan (CPT-11), etoposide and hydroxyurea (HU) and whether exposure to these agents induced features of SIOD. Among 71 SIOD patients, three had non-Hodgkin lymphoma (NHL) and one had osteosarcoma. We did not find evidence of defective NER or NHEJ; however, Smarcal1-deficient mice were hypersensitive to several genotoxic agents. Also, CPT-11, etoposide and HU caused decreased growth and loss of growth plate chondrocytes. These data, which identify an increased prevalence of NHL in SIOD and confirm hypersensitivity to DNA damaging agents in vivo, provide guidance for the management of SIOD patients.
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影响因子：
3.6
作者：
KUBOTA, M;YASUNAGA, M;NISHIGORI, C
通讯作者：
NISHIGORI, C
影响因子：
11.4
作者：
Hirano, Ryuki;Interthal, Heidrun;Boerkoel, Cornelius F.
通讯作者：
Boerkoel, Cornelius F.
影响因子：
10.5
作者：
Bansbach, Carol E.;Betous, Remy;Cortez, David
通讯作者：
Cortez, David
影响因子：
3.6
作者：
Hunter, Kshamta B.;Luecke, Thomas;Boerkoel, Cornelius F.
通讯作者：
Boerkoel, Cornelius F.
影响因子：
2
作者：
Kilic, SS;Donmez, O;Boerkoel, CF
通讯作者：
Boerkoel, CF