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Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes.
Cell Stem Cell ( IF 23.9 ) Pub Date : 2017-09-07 , DOI: 10.1016/j.stem.2017.07.010
Catherine C. Coombs , Ahmet Zehir , Sean M. Devlin , Ashwin Kishtagari , Aijazuddin Syed , Philip Jonsson , David M. Hyman , David B. Solit , Mark E. Robson , José Baselga , Maria E. Arcila , Marc Ladanyi , Martin S. Tallman , Ross L. Levine , Michael F. Berger

Clonal hematopoiesis (CH), as evidenced by recurrent somatic mutations in leukemia-associated genes, commonly occurs among aging human hematopoietic stem cells. We analyzed deep-coverage, targeted, next-generation sequencing (NGS) data of paired tumor and blood samples from 8,810 individuals to assess the frequency and clinical relevance of CH in patients with non-hematologic malignancies. We identified CH in 25% of cancer patients, with 4.5% harboring presumptive leukemia driver mutations (CH-PD). CH was associated with increased age, prior radiation therapy, and tobacco use. PPM1D and TP53 mutations were associated with prior exposure to chemotherapy. CH and CH-PD led to an increased incidence of subsequent hematologic cancers, and CH-PD was associated with shorter patient survival. These data suggest that CH occurs in an age-dependent manner and that specific perturbations can enhance fitness of clonal hematopoietic stem cells, which can impact outcome through progression to hematologic malignancies and through cell-non-autonomous effects on solid tumor biology.

中文翻译:

非血液系统癌症患者中与治疗有关的克隆性造血作用很常见,并且与不良的临床结果相关。

白血病相关基因的反复体细胞突变证明,克隆性造血(CH)通常发生在衰老的人类造血干细胞中。我们分析了来自8810个个体的配对肿瘤和血液样本的深度覆盖,靶向,下一代测序(NGS)数据,以评估非血液系统恶性肿瘤患者CH的发生频率和临床相关性。我们在25%的癌症患者中发现了CH,其中4.5%带有推测的白血病驱动基因突变(CH-PD)。CH与年龄增加,先前的放射治疗和吸烟有关。PPM1D和TP53突变与先前接受化疗有关。CH和CH-PD导致随后的血液系统癌症的发生率增加,而CH-PD与患者生存期缩短有关。
更新日期:2017-08-10
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