Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Bersani F,Lee E,Kharchenko PV,Xu AW,Liu M,Xega K,MacKenzie OC,Brannigan BW,Wittner BS,Jung H,Ramaswamy S,Park PJ,Maheswaran S,Ting DT,Haber DAdoi
10.1073/pnas.1518008112subject
Has Abstractpub_date
2015-12-08 00:00:00pages
15148-53issue
49eissn
0027-8424issn
1091-6490pii
1518008112journal_volume
112pub_type
杂志文章abstract::HLA-A and -B antigens are phosphorylated in transformed lymphoblastoid cells and peripheral blood lymphocytes, both incubated with 32Pi. The phosphate group is attached to HLA-A and -B heavy chain (p44) as identified by immunoprecipitation with anti-beta2-microglobulin IgG, sodium dodecyl sulfate/polyacrylamide gel el...
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