Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aao3130 |
Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer | |
Drost, Jarno1,2,3,10; van Boxtel, Ruben3,4,10; Blokzijl, Francis3,4; Mizutani, Tomohiro1,2,3; Sasaki, Nobuo1,2,3; Sasselli, Valentina1,2,3; de Ligt, Joep3,4; Behjati, Sam5,6; Grolleman, Judith E.7; van Wezel, Tom8; Nik-Zainal, Serena5,9; Kuiper, Roland P.7,10; Cuppen, Edwin3,4; Clevers, Hans1,2,3,10 | |
2017-10-13 | |
发表期刊 | SCIENCE
![]() |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 358期号:6360页码:234-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Netherlands; England |
英文摘要 | Mutational processes underlie cancer initiation and progression. Signatures of these processes in cancer genomes may explain cancer etiology and could hold diagnostic and prognostic value. We developed a strategy that can be used to explore the origin of cancer-associated mutational signatures. We used CRISPR-Cas9 technology to delete key DNA repair genes in human colon organoids, followed by delayed subcloning and whole-genome sequencing. We found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair-deficient colorectal cancers. Application of this strategy to the cancer predisposition gene NTHL1, which encodes a base excision repair protein, revealed a mutational footprint (signature 30) previously observed in a breast cancer cohort. We show that signature 30 can arise from germline NTHL1 mutations. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000412841500051 |
WOS关键词 | BASE-EXCISION-REPAIR ; DNA MISMATCH REPAIR ; COLORECTAL-CANCER ; SOMATIC MUTATIONS ; LIFE-SPAN ; GENOME ; TUMORS ; RATES |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197086 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands; 2.Univ Med Ctr UMC Utrecht, NL-3584 CT Utrecht, Netherlands; 3.UMC Utrecht, Canc Genom Netherlands, NL-3584 CX Utrecht, Netherlands; 4.UMC Utrecht, Dept Genet, Ctr Mol Med, NL-3584 CX Utrecht, Netherlands; 5.Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England; 6.Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England; 7.Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Human Genet, Med Ctr, Nijmegen, Netherlands; 8.Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands; 9.Cambridge Univ Hosp Natl Hlth Serv Fdn Trust, East Anglian Med Genet Serv, Cambridge, England; 10.Princess Maxima Ctr Pediat Oncol, NL-3584 CT Utrecht, Netherlands |
推荐引用方式 GB/T 7714 | Drost, Jarno,van Boxtel, Ruben,Blokzijl, Francis,et al. Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer[J]. SCIENCE,2017,358(6360):234-+. |
APA | Drost, Jarno.,van Boxtel, Ruben.,Blokzijl, Francis.,Mizutani, Tomohiro.,Sasaki, Nobuo.,...&Clevers, Hans.(2017).Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer.SCIENCE,358(6360),234-+. |
MLA | Drost, Jarno,et al."Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer".SCIENCE 358.6360(2017):234-+. |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论