TY  - JOUR
ID  - publicatio35541
TI  - Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma
SP  - 86
A1  -  Biswas Dhruva
A1  -  Liu Yun-Hsin
A1  -  Herrero Javier
A1  -  Snell Daniel M.
A1  -  O?Neill Olga
A1  -  Leonce Daniel
A1  -  Mattsson Johanna
A1  -  Lindberg Amanda
A1  -  Micke Patrick
A1  -  Moldvay Judit
A1  -  Megyesfalvi Zsolt
A1  -  Döme Balazs
A1  -  Fillinger János
A1  -  Nicod Jerome
A1  -  Downward Julian
A1  -  Kollaboráiós szervezet: TRACERx Consortium
A1  -  et al.
Y1  - 2025///
UR  - https://doi.org/10.1038/s43018-024-00883-1
N2  - 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.
VL  - 6
N1  - Online ahead of print. 
Published online: 09 January 2025
EP  - 101
IS  - 1
SN  - 2662-1347
AV  - restricted
JF  - NATURE CANCER
ER  -