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• W2292769011 abstract "// Huaping Xie 1, 2 , P. Sivaramakrishna Rachakonda 2 , Barbara Heidenreich 2 , Eduardo Nagore 3 , Antje Sucker 4 , Kari Hemminki 2, 5 , Dirk Schadendorf 4, 6 , Rajiv Kumar 2 1 Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany 3 Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain 4 Department of Dermatology, University Hospital Essen, Essen, Germany 5 Center for Primary Health Care Research, Lund University, Malmö, Sweden 6 German Cancer Consortium (DKTK), Essen, Germany Correspondence to: Rajiv Kumar, e-mail: r.kumar@dkfz.de Keywords: melanoma, CDKN2A, deletions, break points Received: December 28, 2015    Accepted: February 11, 2016     Published: February 19, 2016 ABSTRACT Genomic locus at chromosome 9p21 that contains the CDKN2A and CDKN2B tumor suppressor genes is inactivated through mutations, deletions and promoter methylation in multiple human cancers. Additionally, the locus encodes an anti-sense RNA ( ANRIL ). Both hemizygous and homozygous deletions at the locus targeting multiple genes are fairly common in different cancers. We in this study investigated breakpoints in five melanoma cell lines, derived from metastasized tumors, with previously identified homozygous deletions using array comparative genomic hybridization (aCGH). For breakpoint mapping, we used primer approximation multiplex PCR (PAMP) and inverse PCR techniques. Our results showed that three cell lines carried complex rearrangements. In two other cell lines, with focal deletions of 141 kb and 181 kb, we identified fusion gene products, involving MTAP and ANRIL . We also confirmed the complex rearrangements and focal deletions in DNA from tumor tissues corresponding to three cell lines. The rapid amplification of 3’cDNA ends (3’RACE) carried out on transcripts resulted in identification of three isoforms of MTAP-ANRIL fusion gene. Screening of cDNA from 64 melanoma cell lines resulted in detection of fusion transcripts in 13 (20%) cell lines that involved exons 4-7 of the MTAP and exon 2 or 5 of the ANRIL genes. We also detected fusion transcripts involving MTAP and ANRIL in two of the seven primary melanoma tumors with focal deletion at the locus. The results from the study, besides identifying complex rearrangements involving CDKN2A locus, show frequent occurrence of fusion transcripts involving MTAP and ANRIL genes." @default.
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• W2292769011 date "2016-02-19" @default.
• W2292769011 modified "2023-10-15" @default.
• W2292769011 title "Mapping of deletion breakpoints at the<i>CDKN2A</i>locus in melanoma: detection of<i>MTAP-ANRIL</i>fusion transcripts" @default.
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• W2292769011 doi "https://doi.org/10.18632/oncotarget.7503" @default.
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