Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers Journal Article
| Authors: | Chatila, W. K.; Walch, H.; Hechtman, J. F.; Moyer, S. M.; Sgambati, V.; Faleck, D. M.; Srivastava, A.; Tang, L.; Benhamida, J.; Ismailgeci, D.; Campos, C.; Wu, F.; Chang, Q.; Vakiani, E.; de Stanchina, E.; Weiser, M. R.; Widmar, M.; Yantiss, R. K.; Shah, M. A.; Bass, A. J.; Stadler, Z. K.; Katz, L. H.; Mellinghoff, I. K.; Sethi, N. S.; Schultz, N.; Ganesh, K.; Kelsen, D.; Yaeger, R. |
| Article Title: | Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers |
| Abstract: | 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. © 2023, The Author(s). |
| Keywords: | genetics; mouse; animal; animals; mice; inflammation; evolution; evolution, molecular; molecular evolution; hyperplasia; genomics; inflammatory bowel diseases; complication; inflammatory bowel disease; cancer; convergent evolution; colitis-associated neoplasms |
| Journal Title: | Nature Communications |
| Volume: | 14 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-01-07 |
| Start Page: | 110 |
| Language: | English |
| DOI: | 10.1038/s41467-022-35592-9 |
| PUBMED: | 36611031 |
| PROVIDER: | scopus |
| PMCID: | PMC9825391 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Rona Yaeger -- Export Date: 1 February 2023 -- Source: Scopus |
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