Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-11

AUTHORS

T J Pugh, W Yu, J Yang, A L Field, L Ambrogio, S L Carter, K Cibulskis, P Giannikopoulos, A Kiezun, J Kim, A McKenna, E Nickerson, G Getz, S Hoffher, Y H Messinger, L P Dehner, C W M Roberts, C Rodriguez-Galindo, G M Williams, C T Rossi, M Meyerson, D A Hill

ABSTRACT

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. More... »

PAGES

5295

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2014.150

DOI

http://dx.doi.org/10.1038/onc.2014.150

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021220375

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24909177


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