| Title: |
Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma |
| Authors: |
Biswas, D.; Liu, Y.-H.; Herrero, J.; Wu, Y.; Moore, D.A.; Karasaki, T.; Grigoriadis, K.; Lu, W.-T.; Veeriah, S.; Naceur-Lombardelli, C.; Magno, N.; Ward, S.; Frankell, A.M.; Hill, M.S.; Colliver, E.; de Carné Trécesson, S.; East, P.; Malhi, A.; Snell, D.M.; O’Neill, O.; Leonce, D.; Mattsson, J.; Lindberg, A.; Micke, P.; Moldvay, J.; Megyesfalvi, Z.; Dome, B.; Fillinger, J.; Nicod, J.; Downward, J.; Szallasi, Z.; Huebner, A.; Richard, C.; Hiley, C.T.; Lim, E.L.; Gimeno-Valiente, F.; Thakkar, K.; Bakir, M.A.; Sivakumar, M.; Usaite, I.; Saghafinia, S.; Vanloo, S.; Harries, S.; Toncheva, A.; Prymas, P.; Mussa, B.; Magala, M.; Keene, E.; Bunkum, A.; Martínez-Ruiz, C.; Puttick, C.; Karagianni, D.; Black, J.R.M.; Thol, K.; McGranahan, N.; Lucas, O.; Bentham, R.; Vendramin, R.; Quezada, S.A.; Zaccaria, S.; Hessey, S.; Bola, S.K.; Liu, W.K.; Zaidi, R.; Patruno, L.; Forster, M.D.; Lee, S.M.; Wilson, G.A.; Rosenthal, R.; Rowan, A.; Bailey, C.; Lee, C.; Enfield, K.S.S.; Angelova, M.; Pich, O.; Murphy, C.; Zagorulya, M.; Leung, M.M.; Marafioti, T.; Borg, E.; Falzon, M.; Khiroya, R.; Jones, T.P.; Benafif, S.; Papadatos-Pastos, D.; Wilson, J.; Ahmad, T.; Dwornik, A.; Karamani, A.; Chain, B.; Pearce, D.R.; Stavrou, G.; Mastrokalos, G.-T.; Lowe, H.L.; Reading, J.L.; Hartley, J.A.; Selvaraju, K.; Ensell, L.; Shah, M.; Litovchenko, M.; Pawlik, P.; Gamble, S.; Ung, S.K.A.; Spanswick, V.; Weeden, C.E.; Grönroos, E.; Goldman, J.; Escudero, M.; Hobson, P.; Boeing, S.; Denner, T.; Barbè, V.; Hill, W.; Naito, Y.; Sahai, E.; Ramsden, Z.; Kassiotis, G.; Noorani, I.; Lester, J.F.; Bajaj, A.; Nakas, A.; Sodha-Ramdeen, A.; Tufail, M.; Scotland, M.; Boyles, R.; Rathinam, S.; Dulloo, S.; Fennell, D.A.; Wilson, C.; Matharu, G.; Shaw, J.A.; Boleti, E.; Cheyne, H.; Khalil, M.; Richardson, S.; Cruickshank, T.; Price, G.; Kerr, K.M.; French, J.; Gilbert, K.; Naidu, B.; Patel, A.J.; Osman, A.; Sangha, M.; Langman, G.; Shackleford, H.; Djearaman, M.; Middleton, G.; Leek, A.; Hodgkinson, J.D.; Totton, N.; Fontaine, E.; Granato, F.; Novasio, J.; Rammohan, K.; Joseph, L.; Bishop, P.; Joshi, V.; Waplington, S.; Atkin, A.; Paiva-Correia, A.; Crosbie, P.; Brown, K.D.; Carter, M.; Chaturvedi, A.; Oliveira, P.; Lindsay, C.R.; Blackhall, F.H.; Summers, Y.; Krebs, M.G.; Tugwood, J.; Dive, C.; Aerts, H.J.W.L.; Schwarz, R.F.; Kaufmann, T.L.; Van Loo, P.; Castignani, C.; Salgado, R.; Diossy, M.; Demeulemeester, J.; Beck, S.; Nye, E.; Stone, R.K.; Rane, J.K.; Kittel, J.; Haase, K.; Koh, K.; Scott, R.; Peggs, K.S.; Hoogenboom, E.M.; Monk, F.; Holding, J.W.; Choudhary, J.; Bhakhri, K.; Gorman, P.; Stephens, R.C.M.; Wong, Y.N.S.; Pisciella, M.C.; Bandula, S.; Watkins, T.B.K.; Veiga, C.; Royle, G.; Collins-Fekete, C.-A.; Fraioli, F.; Ashford, P.; Procter, A.J.; Ahmed, A.; Taylor, M.N.; Nair, A.; Lawrence, D.; Patrini, D.; Navani, N.; Thakrar, R.M.; Janes, S.M.; Kaplar, Z.; Hackshaw, A.; Pilotti, C.; Leslie, R.; Hacker, A.-M.; Smith, S.; Walker, A.; Grapa, A.; Zhang, H.; AbdulJabbar, K.; Pan, X.; Yuan, Y.; Chuter, D.; MacKenzie, M.; Chee, S.; Georg, P.; Alzetani, A.; Cave, J.; Lim, E.; De Sousa, P.; Jordan, S.; Rice, A.; Raubenheimer, H.; Bhayani, H.; Ambrose, L.; Devaraj, A.; Chavan, H.; Begum, S.; Buderi, S.I.; Kaniu, D.; Malima, M.; Booth, S.; Nicholson, A.G.; Fernandes, N.; Shah, P.; Proli, C.; Hewish, M.; Danson, S.; Shackcloth, M.J.; Robinson, L.; Russell, P.; Blyth, K.G.; Kidd, A.; Dick, C.; Le Quesne, J.; Kirk, A.; Asif, M.; Bilancia, R.; Kostoulas, N.; Whiteley, J.; Thomas, M.; Jamal-Hanjani, M.; Kanu, N.; Birkbak, N.J.; Swanton, C. |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2025 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
2662-1347 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/224430/1/s43018-024-00883-1.pdf; Biswas, D. orcid.org/0000-0001-9141-5188 , Liu, Y.-H. orcid.org/0009-0001-1508-5276 , Herrero, J. orcid.org/0000-0001-7313-717X et al. (267 more authors) (2025) Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma. Nature Cancer, 6. pp. 86-101. ISSN: 2662-1347 |
| DOI: |
10.1038/s43018-024-00883-1 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/224430/; https://doi.org/10.1038/s43018-024-00883-1 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.7B70DF6A |
| Database: |
BASE |