Tracking the Evolution of Non-Small-Cell Lung Cancer.

Détails

ID Serval
serval:BIB_B5C92AE7BF35
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tracking the Evolution of Non-Small-Cell Lung Cancer.
Périodique
The New England journal of medicine
Auteur(s)
Jamal-Hanjani M., Wilson G.A., McGranahan N., Birkbak N.J., Watkins TBK, Veeriah S., Shafi S., Johnson D.H., Mitter R., Rosenthal R., Salm M., Horswell S., Escudero M., Matthews N., Rowan A., Chambers T., Moore D.A., Turajlic S., Xu H., Lee S.M., Forster M.D., Ahmad T., Hiley C.T., Abbosh C., Falzon M., Borg E., Marafioti T., Lawrence D., Hayward M., Kolvekar S., Panagiotopoulos N., Janes S.M., Thakrar R., Ahmed A., Blackhall F., Summers Y., Shah R., Joseph L., Quinn A.M., Crosbie P.A., Naidu B., Middleton G., Langman G., Trotter S., Nicolson M., Remmen H., Kerr K., Chetty M., Gomersall L., Fennell D.A., Nakas A., Rathinam S., Anand G., Khan S., Russell P., Ezhil V., Ismail B., Irvin-Sellers M., Prakash V., Lester J.F., Kornaszewska M., Attanoos R., Adams H., Davies H., Dentro S., Taniere P., O'Sullivan B., Lowe H.L., Hartley J.A., Iles N., Bell H., Ngai Y., Shaw J.A., Herrero J., Szallasi Z., Schwarz R.F., Stewart A., Quezada S.A., Le Quesne J., Van Loo P., Dive C., Hackshaw A., Swanton C.
Collaborateur(s)
TRACERx Consortium
Contributeur(s)
Czyzewska-Khan J., Laycock J., Bosshard-Carter L., Goh G., Gorman P., Murugaesu N., Hynds R.E., Goldman J., Stone R.K., Denner T., Elgar G., Ward S., Biggs J., Costa M., Begum S., Phillimore B., Nye E., Graca S., Al Bakir M., Joshi K., Furness A., Ben Aissa A., Wong Y.N., Georgiou A., Patrini D., Simeon C., Hector G., Smith A., Aranda M., Novelli M., Oukrif D., Papadatos-Pastos D., Carnell D., Mendes R., George J., Navani N., Taylor M., Shaw P., Choudhary J., Califano R., Taylor P., Krysiak P., Rammohan K., Fontaine E., Booton R., Evison M., Moss S., Idries F., Bishop P., Chaturved A., Doran H., Leek A., Harrison P., Moore K., Waddington R., Novasio J., Rogan J., Smith E., Tugwood J., Brady G., Rothwell D.G., Chemi F., Pierce J., Gulati S., Bellamy M., Bancroft H., Kerr A., Kadiri S., Webb J., Djearaman M., Monteiro W., Marshall H., Nelson L., Bennett J., Riley J., Primrose L., Martinson L., Amadi A., Palmer S., Miller J., Buchan K., Edwards A., Morgan F., Lock S., Verjee A., MacKenzie M., Wilcox M., Smith S., Gower N., Ottensmeier C., Chee S., Johnson B., Alzetani A., Shaw E., Lim E., De Sousa P., Barbosa M.T., Bowman A., Jordan S., Rice A., Raubenheimer H., Proli C., Cufari M.E., Ronquillo J.C., Kwayie A., Bhayani H., Hamilton M., Bakar Y., Mensah N., Ambrose L., Devaraj A., Buderi S., Finch J., Azcarate L., Chavan H., Green S., Mashinga H., Nicholson A.G., Lau K., Sheaff M., Schmid P., Conibear J., Light T., Horey T., Danson S., Bury J., Edwards J., Hill J., Matthews S., Kitsanta Y., Suvarna K., Fisher P., Keerio A.D., Shackcloth M., Gosney J., Postmus P., Feeney S., Asante-Siaw J., Constatin T., Salari R., Sponer N., Naik A., Zimmermann B., Aerts H.J., Dessimoz C., Peggs K.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Statut éditorial
Publié
Date de publication
01/06/2017
Peer-reviewed
Oui
Volume
376
Numéro
22
Pages
2109-2121
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC.
In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival.
We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10 <sup>-4</sup> ), which remained significant in multivariate analysis.
Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).
Mots-clé
Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/mortality, Chromosomal Instability, DNA Copy Number Variations, Disease-Free Survival, Evolution, Molecular, Exome, Female, Genetic Heterogeneity, Humans, Lung Neoplasms/genetics, Lung Neoplasms/mortality, Male, Mutation, Neoplasm Recurrence, Local/genetics, Phylogeny, Prognosis, Prospective Studies, Risk Factors, Sequence Analysis, DNA/methods
Pubmed
Web of science
Création de la notice
23/01/2020 16:29
Dernière modification de la notice
22/01/2021 7:26
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