%0 Journal Article
%@ 2662-1347
%A  Biswas Dhruva
%A  Liu Yun-Hsin
%A  Herrero Javier
%A  Snell Daniel M.
%A  O’Neill Olga
%A  Leonce Daniel
%A  Mattsson Johanna
%A  Lindberg Amanda
%A  Micke Patrick
%A  Moldvay Judit
%A  Megyesfalvi Zsolt
%A  Döme Balazs
%A  Fillinger János
%A  Nicod Jerome
%A  Downward Julian
%A  Kollaboráiós szervezet: TRACERx Consortium
%A  et al.
%A Tüdőgyógyászati Klinika SZTE / SZAOK TGYK [2023-],
%D 2025
%F publicatio:35541
%J NATURE CANCER
%N 1
%P 86-101
%T Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma
%U http://publicatio.bibl.u-szeged.hu/35541/
%V 6
%X 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.
%Z Online ahead of print.  Published online: 09 January 2025