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Isobe, Tomoya; Seki, Masafumi; Yoshida, Kenichi; Sekiguchi, Masahiro; Shiozawa, Yusuke; Shiraishi, Yuichi; Kimura, Shunsuke; Yoshida, Misa; Inoue, Yoshikage; Yokoyama, Akira; Kakiuchi, Nobuyuki; Suzuki, Hiromichi; Kataoka, Keisuke; Sato, Yusuke; Kawai, Tomoko; Chiba, Kenichi; Tanaka, Hiroko; Shimamura, Teppei; Kato, Motohiro; Iguchi, Akihiro; Hama, Asahito; Taguchi, Tomoaki; Akiyama, Masaharu; Fujimura, Junya; Inoue, Akiko; Ito, Tsuyoshi; Deguchi, Takao; Kiyotani, Chikako; Iehara, Tomoko; Hosoi, Hajime; Oka, Akira; Sanada, Masashi; Tanaka, Yukichi; Hata, Kenichiro; Miyano, Satoru; Ogawa, Seishi; Takita, Junko
Cancer research, 02/2018, Letnik: 78, Številka: 4Journal Article
Pancreatoblastoma is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multiomics study of whole-exome and RNA sequencing as well as genome-wide copy number and methylation analyses of ten pancreatoblastoma cases. The pancreatoblastoma genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of (90%) and copy-neutral loss of heterozygosity (CN-LOH) of (10%). In addition, imprinting dysregulation of as a consequence of CN-LOH (80%), gain of paternal allele (10%), and gain of methylation (10%) was universally detected. At the transcriptome level, pancreatoblastoma exhibited an expression profile characteristic of early pancreas progenitor-like cells along with upregulation of the R-spondin/LGR5/RNF43 module. Our results offer a comprehensive description of the molecular basis for pancreatoblastoma and highlight rational therapeutic targets for its treatment. Molecular genetic analysis of a rare untreatable pediatric tumor reveals Wnt/IGF2 aberrations and features of early pancreas progenitor-like cells, suggesting cellular origins and rational strategies for therapeutic targeting. .
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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