Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Carcinoma, Transitional Cell
/ genetics
Circulating Tumor DNA
/ blood
Female
Genomics
Humans
Male
Middle Aged
Mutation
Plasma
Prognosis
Receptor, ErbB-2
/ genetics
Retrospective Studies
Survival Analysis
Urinary Bladder
Urinary Bladder Neoplasms
/ blood
Xeroderma Pigmentosum Group D Protein
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 01 2021
08 01 2021
Historique:
received:
03
04
2020
accepted:
07
12
2020
entrez:
9
1
2021
pubmed:
10
1
2021
medline:
29
1
2021
Statut:
epublish
Résumé
Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
Identifiants
pubmed: 33420073
doi: 10.1038/s41467-020-20493-6
pii: 10.1038/s41467-020-20493-6
pmc: PMC7794518
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Xeroderma Pigmentosum Group D Protein
EC 3.6.4.12
ERCC2 protein, human
EC 5.99.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
184Subventions
Organisme : CIHR
Pays : Canada
Commentaires et corrections
Type : CommentIn
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