Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer

被引:130
作者
Bersani, Francesca [1 ]
Lee, Eunjung [2 ,3 ]
Kharchenko, Peter V. [2 ,4 ]
Xu, Andrew W. [2 ]
Liu, Mingzhu [1 ,5 ]
Xega, Kristina [1 ]
MacKenzie, Olivia C. [1 ]
Brannigan, Brian W. [1 ]
Wittner, Ben S. [1 ]
Jung, Hyunchul [6 ]
Ramaswamy, Sridhar [1 ,7 ]
Park, Peter J. [2 ,3 ,8 ]
Maheswaran, Shyamala [1 ,9 ]
Ting, David T. [1 ,7 ]
Haber, Daniel A. [1 ,5 ,7 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA
[2] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA
[4] Childrens Hosp, Hematol Oncol Program, Boston, MA 02115 USA
[5] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
[6] Samsung Med Ctr, Seoul 135710, South Korea
[7] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA
[8] Childrens Hosp, Informat Program, Boston, MA 02115 USA
[9] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA
基金
英国惠康基金;
关键词
satellites; reverse transcription; repeats; cancer; NONCODING RNAS; HYPOMETHYLATION; HETEROCHROMATIN; TRANSCRIPTION; SEQUENCES; ANTIBODY; HYBRIDS; LINE-1;
D O I
10.1073/pnas.1518008112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Aberrant transcription of the pericentromeric human satellite II (HSATII) repeat is present in a wide variety of epithelial cancers. In deriving experimental systems to study its deregulation, we observed that HSATII expression is induced in colon cancer cells cultured as xenografts or under nonadherent conditions in vitro, but it is rapidly lost in standard 2D cultures. Unexpectedly, physiological induction of endogenous HSATII RNA, as well as introduction of synthetic HSATII transcripts, generated cDNA intermediates in the form of DNA/RNA hybrids. Single molecule sequencing of tumor xenografts showed that HSATII RNA-derived DNA (rdDNA) molecules are stably incorporated within pericentromeric loci. Suppression of RT activity using small molecule inhibitors reduced HSATII copy gain. Analysis of whole-genome sequencing data revealed that HSATII copy number gain is a common feature in primary human colon tumors and is associated with a lower overall survival. Together, our observations suggest that cancer-associated derepression of specific repetitive sequences can promote their RNA-driven genomic expansion, with potential implications on pericentromeric architecture.
引用
收藏
页码:15148 / 15153
页数:6
相关论文
共 33 条
[1]   Telomeric repeat-containing RNA and RNA surveillance factors at mammalian chromosome ends [J].
Azzalin, Claus M. ;
Reichenbach, Patrick ;
Khoriauli, Lela ;
Giulotto, Elena ;
Lingner, Joachim .
SCIENCE, 2007, 318 (5851) :798-801
[2]   Noisy silence Non-coding RNA and heterochromatin formation at repetitive elements [J].
Bierhoff, Holger ;
Postepska-Igielska, Anna ;
Grummt, Ingrid .
EPIGENETICS, 2014, 9 (01) :53-61
[3]   KDM4A Lysine Demethylase Induces Site-Specific Copy Gain and Rereplication of Regions Amplified in Tumors [J].
Black, Joshua C. ;
Manning, Amity L. ;
Van Rechem, Capucine ;
Kim, Jaegil ;
Ladd, Brendon ;
Cho, Juok ;
Pineda, Cristiana M. ;
Murphy, Nancy ;
Daniels, Danette L. ;
Montagna, Cristina ;
Lewis, Peter W. ;
Glass, Kimberly ;
Allis, C. David ;
Dyson, Nicholas J. ;
Getz, Gad ;
Whetstine, Johnathan R. .
CELL, 2013, 154 (03) :541-555
[4]   CHARACTERIZATION OF MONOCLONAL-ANTIBODY TO DNA.RNA AND ITS APPLICATION TO IMMUNODETECTION OF HYBRIDS [J].
BOGUSLAWSKI, SJ ;
SMITH, DE ;
MICHALAK, MA ;
MICKELSON, KE ;
YEHLE, CO ;
PATTERSON, WL ;
CARRICO, RJ .
JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (01) :123-130
[5]   Accumulation of small murine minor satellite transcripts leads to impaired centromeric architecture and function [J].
Bouzinba-Segard, Haniaa ;
Guais, Adeline ;
Francastel, Claire .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (23) :8709-8714
[6]   A new class of retroviral and satellite encoded small RNAs emanates from mammalian centromeres [J].
Carone, Dawn M. ;
Longo, Mark S. ;
Ferreri, Gianni C. ;
Hall, Laura ;
Harris, Melissa ;
Shook, Nicole ;
Bulazel, Kira V. ;
Carone, Benjamin R. ;
Obergfell, Craig ;
O'Neill, Michael J. ;
O'Neill, Rachel J. .
CHROMOSOMA, 2009, 118 (01) :113-125
[7]   Mouse major satellite DNA is prone to eccDNA formation via DNA Ligase IV-dependent pathway [J].
Cohen, Z. ;
Bacharach, E. ;
Lavi, S. .
ONCOGENE, 2006, 25 (33) :4515-4524
[8]   TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY [J].
COUNTER, CM ;
AVILION, AA ;
LEFEUVRE, CE ;
STEWART, NG ;
GREIDER, CW ;
HARLEY, CB ;
BACCHETTI, S .
EMBO JOURNAL, 1992, 11 (05) :1921-1929
[9]   Effect of reverse transcriptase inhibitors on LINE-1 and Ty1 reverse transcriptase activities and on LINE-1 retrotransposition [J].
Dai, Lixin ;
Huang, Qing ;
Boeke, Jef D. .
BMC BIOCHEMISTRY, 2011, 12
[10]   DNA hypomethylation in cancer cells [J].
Ehrlich, Melanie .
EPIGENOMICS, 2009, 1 (02) :239-259