Subclonal mutation selection in mouse lymphomagenesis identifies known cancer loci and suggests novel candidates

dc.creatorWebster, Philip
dc.creatorDawes, Joanna C.
dc.creatorDewchand, Hamlata
dc.creatorTakacs, Katalin
dc.creatorLadarola, Barbara
dc.creatorBolt, Bruce J.
dc.creatorCaceres, Juan J.
dc.creatorKaczor, Jakub
dc.creatorDharmalingam, Gopuraja
dc.creatorDore, Marian
dc.creatorGame, Laurence
dc.creatorAdejumo, Thomas
dc.creatorElliott, James
dc.creatorNaresh, Kikkeri
dc.creatorKarimi, Mohammad
dc.creatorRekopoulou, Katerina
dc.creatorTan, Ge
dc.creatorPaccanaro, Alberto
dc.creatorUren, Anthony G.
dc.date2022-04-06T21:57:20Z
dc.date2022-04-06T21:57:20Z
dc.date2018
dc.date.accessioned2023-09-25T13:31:31Z
dc.date.available2023-09-25T13:31:31Z
dc.identifierhttp://hdl.handle.net/20.500.14066/2833
dc.identifier10.1038/s41467-018-05069-9
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8807437
dc.descriptionDetermining 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.
dc.descriptionCONACYT – Consejo Nacional de Ciencia y Tecnología
dc.descriptionPROCIENCIA
dc.languageeng
dc.relation14-INV-088
dc.rightsopen access
dc.subject1301 I+D en relación con las Ciencias naturales
dc.subjectSUBCLONAL MUTATION
dc.subjectGENOTYPIC AND PHENOTYPIC FEATURES
dc.subjectCANCER GENES
dc.subjectLEUCEMIA
dc.subjectBIOLOGIA MOLECULAR
dc.subjectBIOLOGIA
dc.titleSubclonal mutation selection in mouse lymphomagenesis identifies known cancer loci and suggests novel candidates
dc.typeresearch article


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