Human Chromosomal Translocations at CpG Sites and a Theoretical Basis for Their Lineage and Stage Specificity

被引：183

作者：

Tsai, Albert G. ^{[1
,2
,3
,4
,5
]}

Lu, Haihui ^{[1
,2
,3
,4
,5
]}

Raghavan, Sathees C. ^{[1
,2
,3
,4
,5
]}

Muschen, Markus ^{[6
,7
]}

Hsieh, Chih-Lin ^{[1
,2
,3
,4
,5
]}

Lieber, Michael R. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA 90089 USA

[2] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA

[3] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Mol Microbiol & Immunol, Los Angeles, CA 90089 USA

[4] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA

[5] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biol Sci, Los Angeles, CA 90089 USA

[6] Univ So Calif, Childrens Hosp Los Angeles, Kenneth Norris Jr Comprehens Canc Ctr, Dept Pediat, Los Angeles, CA 90027 USA

[7] Univ So Calif, Childrens Hosp Los Angeles, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90027 USA

来源：

CELL | 2008年 / 135卷 / 06期

关键词：

D O I：

10.1016/j.cell.2008.10.035

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：

We have assembled, annotated, and analyzed a database of over 1700 breakpoints from the most common chromosomal rearrangements in human leukemias and lymphomas. Using this database, we show that although the CpG dinucleotide constitutes only 1% of the human genome, it accounts for 40%-70% of breakpoints at pro-B/pre-B stage translocation regions-specifically, those near the bcl-2, bcl-1, and E2A genes. We do not observe CpG hotspots in rearrangements involving lymphoid-myeloid progenitors, mature B cells, or T cells. The stage specificity, lineage specificity, CpG targeting, and unique breakpoint distributions at these cluster regions may be explained by a lesion-specific double-strand breakage mechanism involving the RAG complex acting at AID-deaminated methyl-CpGs.

引用

页码：1130 / 1142

页数：13

共 72 条

[1] IMMUNOGLOBULIN HEAVY-CHAIN EXPRESSION AND CLASS SWITCHING IN A MURINE LEUKEMIA-CELL LINE [J].