RT Journal
A1 Shah, Maitri Y.
A1 Ferracin, Manuela
A1 Pileczki, Valentina
A1 Chen, Baoqing
A1 Redis, Roxana
A1 Fabris, Linda
A1 Zhang, Xinna
A1 Ivan, Cristina
A1 Shimizu, Masayoshi
A1 Rodriguez-Aguayo, Cristian
A1 Dragomir, Mihnea
A1 Van Roosbroeck, Katrien
A1 Almeida, Maria Ines
A1 Ciccone, Maria
A1 Nedelcu, Daniela
A1 Cortez, Maria Angelica
A1 Manshouri, Taghi
A1 Calin, Steliana
A1 Muftuoglu, Muharrem
A1 Banerjee, Pinaki P.
A1 Badiwi, Mustafa H.
A1 Parker-Thornburg, Jan
A1 Multani, Asha
A1 Welsh, James William
A1 Estecio, Marcos Roberto
A1 Ling, Hui
A1 Tomuleasa, Ciprian
A1 Dima, Delia
A1 Yang, Hui
A1 Alvarez, Hector
A1 You, M. James
A1 Radovich, Milan
A1 Shpall, Elizabeth
A1 Fabbri, Muller
A1 Rezvani, Katy
A1 Girnita, Leonard
A1 Berindan-Neagoe, Ioana
A1 Maitra, Anirban
A1 Verstovsek, Srdan
A1 Fodde, Riccardo
A1 Bueso-Ramos, Carlos
A1 Gagea, Mihai
A1 Manero, Guillermo Garcia
A1 Calin, George A.
T1 Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
JF Genome Research 
JO Genome Research 
YR 2018 
FD April 01 
VO 28 
IS 4 
SP 432 
OP 447 
DO 10.1101/gr.225128.117 
UL http://genome.cshlp.org/content/28/4/432.abstract 
AB The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.