Translocation-Capture Sequencing Reveals the Extent and Nature of Chromosomal Rearrangements in B Lymphocytes

被引：281

作者：

Klein, Isaac A. ^{[2
]}

Resch, Wolfgang ^{[5
]}

Jankovic, Mila ^{[2
]}

Oliveira, Thiago ^{[2
,6
,7
]}

Yamane, Arito ^{[1
,5
]}

Nakahashi, Hirotaka ^{[1
,5
]}

Di Virgilio, Michela ^{[2
]}

Bothmer, Anne ^{[2
]}

Nussenzweig, Andre ^{[4
]}

Robbiani, Davide F. ^{[2
]}

Casellas, Rafael ^{[1
,5
]}

Nussenzweig, Michel C. ^{[2
,3
]}

机构：

[1] NCI, Ctr Canc Res, Bethesda, MD 20892 USA

[2] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA

[3] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA

[4] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA

[5] NIAMSD, NIH, Bethesda, MD 20892 USA

[6] Univ Sao Paulo, Natl Inst Sci & Technol Stem Cells & Cell Therapy, Dept Genet, Med Sch Ribeirao Preto, BR-14051140 Ribeirao Preto, SP, Brazil

[7] Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, SP, Brazil

来源：

CELL | 2011年 / 147卷 / 01期

基金：

美国国家卫生研究院;

关键词：

CLASS-SWITCH RECOMBINATION; CYTIDINE DEAMINASE AID; SOMATIC HYPERMUTATION; CELL LYMPHOMA; C-MYC; DNA BREAKS; FOLLICULAR LYMPHOMA; GENOMIC INSTABILITY; CANCER GENOME; BCL6; GENE;

D O I：

10.1016/j.cell.2011.07.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chromosomal rearrangements, including translocations, require formation and joining of DNA double strand breaks (DSBs). These events disrupt the integrity of the genome and are frequently involved in producing leukemias, lymphomas and sarcomas. Despite the importance of these events, current understanding of their genesis is limited. To examine the origins of chromosomal rearrangements we developed-Translocation Capture Sequencing (TC-Seq), a method to document chromosomal rearrangements genome-wide, in primary cells. We examined over 180,000 rearrangements obtained from 400 million B lymphocytes, revealing that proximity between DSBs, transcriptional activity and chromosome territories are key determinants of genome rearrangement. Specifically, rearrangements tend to occur in cis and to transcribed genes. Finally, we find that activation-induced cytidine deaminase (AID) induces the rearrangement of many genes found as translocation partners in mature B cell lymphoma.

引用

页码：95 / 106

页数：12

共 66 条

[1] The connection between transcription and genomic instability [J].