relation: http://publicatio.bibl.u-szeged.hu/35541/
title: Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma
creator:  Biswas Dhruva
creator:  Liu Yun-Hsin
creator:  Herrero Javier
creator:  Snell Daniel M.
creator:  O’Neill Olga
creator:  Leonce Daniel
creator:  Mattsson Johanna
creator:  Lindberg Amanda
creator:  Micke Patrick
creator:  Moldvay Judit
creator:  Megyesfalvi Zsolt
creator:  Döme Balazs
creator:  Fillinger János
creator:  Nicod Jerome
creator:  Downward Julian
creator:  Kollaboráiós szervezet: TRACERx Consortium
creator:  et al.
subject: 03.02. Klinikai orvostan
description: Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study. We prospectively validate the survival association of a clonal expression biomarker, Outcome Risk Associated Clonal Lung Expression (ORACLE), in combination with clinicopathological risk factors, and in stage I disease. We expand our mechanistic understanding, discovering that clonal transcriptional signals are detectable before tissue invasion, act as a molecular fingerprint for lethal metastatic clones and predict chemotherapy sensitivity. Lastly, we find that ORACLE summarizes the prognostic information encoded by genetic evolutionary measures, including chromosomal instability, as a concise 23-transcript assay.
date: 2025
type: Folyóiratcikk
type: PeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/35541/7/35681466.pdf
format: text
identifier: http://publicatio.bibl.u-szeged.hu/35541/1/Nature.pdf
identifier:     Biswas Dhruva;  Liu Yun-Hsin;  Herrero Javier;  Snell Daniel M.;  O’Neill Olga;  Leonce Daniel;  Mattsson Johanna;  Lindberg Amanda;  Micke Patrick;  Moldvay Judit;  Megyesfalvi Zsolt;  Döme Balazs;  Fillinger János;  Nicod Jerome;  Downward Julian;  Kollaboráiós szervezet: TRACERx Consortium;  et al.: Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.   NATURE CANCER, 6 (1).  pp. 86-101.  ISSN 2662-1347 (2025)     
identifier: doi:10.1038/s43018-024-00883-1
relation: https://doi.org/10.1038/s43018-024-00883-1
relation: 35681466
language: eng