小柯机器人

荷兰Princess Máxima儿童肿瘤中心Ruben van Boxtel、Mirjam Belderbos等研究人员合作发现，抗病毒治疗可在移植受者的癌症中引起独特的突变特征。相关论文于2021年9月07日在线发表在《细胞—干细胞》杂志上。

研究人员利用全基因组测序来描述人类造血干细胞移植受者及其捐赠者的造血干细胞和祖先细胞(HSPC)的突变负担。研究人员证明大多数移植的HSPC并没有显示出突变积累的改变。然而，在一些造血干细胞受者中，研究人员发现多个HSPC在移植后突变负担增加。这种增加可归因于抗病毒药物更昔洛韦引起的独特突变特征。

使用机器学习的方法，研究人员在生命早期接受造血干细胞移植或固体器官移植者的癌症基因组中检测到这种特征。核苷类似物的抗病毒治疗可导致移植受者的诱变性增强，这可能最终导致与治疗有关的致癌。

据悉，遗传不稳定性是干细胞在再生医学中成功应用的一个主要问题。然而，人类最常用的干细胞疗法，即造血干细胞移植(HSCT)，其突变后果仍是未知的。

附：英文原文

Title: Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients

Author: Jurrian K. de Kanter, Flavia Peci, Eline Bertrums, Axel Rosendahl Huber, Anas van Leeuwen, Markus J. van Roosmalen, Freek Manders, Mark Verheul, Rurika Oka, Arianne M. Brandsma, Marc Bierings, Mirjam Belderbos, Ruben van Boxtel

Issue&Volume: September 07, 2021

Abstract: Genetic instability is a major concern for successful application of stem cells in regenerative medicine. However, the mutational consequences of the most applied stem cell therapy in humans, hematopoietic stem cell transplantation (HSCT), remain unknown. Here we characterized the mutation burden of hematopoietic stem and progenitor cells (HSPCs) of human HSCT recipients and their donors using whole-genome sequencing. We demonstrate that the majority of transplanted HSPCs did not display altered mutation accumulation. However, in some HSCT recipients, we identified multiple HSPCs with an increased mutation burden after transplantation. This increase could be attributed to a unique mutational signature caused by the antiviral drug ganciclovir. Using a machine learning approach, we detected this signature in cancer genomes of individuals who received HSCT or solid organ transplantation earlier in life. Antiviral treatment with nucleoside analogs can cause enhanced mutagenicity in transplant recipients, which may ultimately contribute to therapy-related carcinogenesis.

DOI: 10.1016/j.stem.2021.07.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00337-4

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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