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Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers

ABSTRACT: Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers

PROVIDER: PRJNA908740 | ENA |

REPOSITORIES: ENA

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Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers [Proj_07182_Z]

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Project description:Inflammation has long been recognized to contribute to cancer development, particularly across the gastrointestinal tract. Patients with inflammatory bowel disease have an increased risk for bowel cancers, and it has been posited that a field of genetic changes may underlie this risk. Here, we define the clinical features, genomic landscape, and germline alterations in 174 patients with colitis-associated cancers and sequenced 29 synchronous or isolated dysplasia. TP53 alterations, an early and highly recurrent event in colitis-associated cancers, occur in half of dysplasia, largely as convergent evolution of independent events. Wnt pathway alterations are infrequent, and our data suggest transcriptional rewiring away from Wnt. Sequencing of multiple dysplasia/cancer lesions from mouse models and patients demonstrates rare shared alterations between lesions. These findings suggest neoplastic bowel lesions developing in a background of inflammation experience lineage plasticity away from Wnt activation early during tumorigenesis and largely occur as genetically independent events. Colitis-associated cancers (CACs) develop in patients with inflammatory bowel disease and have distinct genomic features compared to sporadic colorectal cancers. Here, the authors characterize the genomic alterations of CAC tumors and dysplasia, finding decreased Wnt signaling and a lack of shared early genetic steps.

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Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers

Project description:This SuperSeries is composed of the SubSeries listed below.

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