Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences
| Autor: | Elizabeth Nickerson, Yoav H. Messinger, Charles W. M. Roberts, Jaegil Kim, Kristian Cibulskis, A L Field, P Giannikopoulos, Gaddy Getz, Louis P. Dehner, Weiying Yu, Lauren Ambrogio, Scott L. Carter, Carlos Rodriguez-Galindo, Adam Kiezun, Matthew Meyerson, Aaron McKenna, S Hoffher, Jiandong Yang, D. A. Hill, Gretchen M. Williams, Trevor J. Pugh, Christopher T. Rossi |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Proto-Oncogene Proteins B-raf Ribonuclease III Cancer Research Lung Neoplasms DNA Copy Number Variations Pleuropulmonary blastoma Biology medicine.disease_cause Germline GTP Phosphohydrolases DEAD-box RNA Helicases Genetics medicine Humans Missense mutation Exome Molecular Biology Exome sequencing Oligonucleotide Array Sequence Analysis DICER1 Syndrome Mutation Base Sequence Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Membrane Proteins Sequence Analysis DNA medicine.disease Immunohistochemistry Gene Expression Regulation Neoplastic Pulmonary Blastoma MicroRNAs Cancer research Chromosomes Human Pair 5 Nucleic Acid Conformation Female Original Article Tumor Suppressor Protein p53 |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/onc.2014.150 |
| Popis: | Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer. |
| Databáze: | OpenAIRE |
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