RT Journal Article
T1 Subclonal mutation selection in mouse lymphomagenesis identifies known cancer loci and suggests novel candidates
A1 Webster, Philip
A1 Dawes, Joanna C.
A1 Dewchand, Hamlata
A1 Takacs, Katalin
A1 Ladarola, Barbara
A1 Bolt, Bruce J.
A1 Caceres, Juan J.
A1 Kaczor, Jakub
A1 Dharmalingam, Gopuraja
A1 Dore, Marian
A1 Game, Laurence
A1 Adejumo, Thomas
A1 Elliott, James
A1 Naresh, Kikkeri
A1 Karimi, Mohammad
A1 Rekopoulou, Katerina
A1 Tan, Ge
A1 Paccanaro, Alberto
A1 Uren, Anthony G.
AB 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.
YR 2018
FD 2018
LK http://hdl.handle.net/20.500.14066/2833
UL http://hdl.handle.net/20.500.14066/2833
LA eng
NO CONACYT – Consejo Nacional de Ciencia y Tecnología
DS MINDS@UW
RD 04-nov-2024