UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer

Ganguli, P; Basanta, CC; Acha-Sagredo, A; Misetic, H; Armero, M; Mendez, A; Zahra, A; ... Ciccarelli, FD; + view all (2025) Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer. Nature Cancer 10.1038/s43018-024-00876-0. (In press). Green open access

[thumbnail of 2025 Ganguli et al - Nature Cancer.pdf]
Preview
Text
2025 Ganguli et al - Nature Cancer.pdf - Published Version

Download (5MB) | Preview

Abstract

CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data. Despite its cancer driver role, CDKN2A loss in BE prevents EAC initiation by counterselecting subsequent TP53 alterations. 9p21 gene co-deletions predict poor patient survival in EAC but not BE through context-dependent effects on cell cycle, oxidative phosphorylation and interferon response. Immune quantifications using bulk transcriptome, RNAscope and high-dimensional tissue imaging showed that IFNE loss reduces immune infiltration in BE, but not EAC. Mechanistically, CDKN2A loss suppresses the maintenance of squamous epithelium, contributing to a more aggressive phenotype. Our study demonstrates context-dependent roles of cancer genes during disease evolution, with consequences for cancer detection and patient management.

Type: Article
Title: Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s43018-024-00876-0
Publisher version: https://doi.org/10.1038/s43018-024-00876-0
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10203522
Downloads since deposit
Loading...
1Download
Download activity - last month
Loading...
Download activity - last 12 months
Loading...
Downloads by country - last 12 months
Loading...

Archive Staff Only

View Item View Item