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1.
Nat Commun ; 10(1): 1167, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30842421

RESUMO

The original version of this Article contained an error in the hyperlink for the online repository http://mulvdb.org which was incorrectly given as http://mulv.lms.mrc.ac.uk. This has been corrected in both the PDF and HTML versions of the Article.

2.
Nat Commun ; 9(1): 2649, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29985390

RESUMO

Determining whether recurrent but rare cancer mutations are bona fide driver mutations remains a bottleneck in cancer research. Here we present the most comprehensive analysis of murine leukemia virus-driven lymphomagenesis produced to date, sequencing 700,000 mutations from >500 malignancies collected at time points throughout tumor development. This scale of data allows novel statistical approaches for identifying selected mutations and yields a high-resolution, genome-wide map of the selective forces surrounding cancer gene loci. We also demonstrate negative selection of mutations that may be deleterious to tumor development indicating novel avenues for therapy. Screening of two BCL2 transgenic models confirmed known drivers of human non-Hodgkin lymphoma, and implicates novel candidates including modifiers of immunosurveillance and MHC loci. Correlating mutations with genotypic and phenotypic features independently of local variance in mutation density also provides support for weakly evidenced cancer genes. An online resource http://mulv.lms.mrc.ac.uk allows customized queries of the entire dataset.


Assuntos
Loci Gênicos/genética , Predisposição Genética para Doença/genética , Linfoma/genética , Mutação , Animais , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Células HEK293 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Vírus da Leucemia Murina/genética , Vírus da Leucemia Murina/fisiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese Insercional
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