Noninvasive Detection of Microsatellite Instability and High Tumor Mutation Burden in Cancer Patients Treated with PD-1 Blockade.
Antineoplastic Agents, Immunological
/ therapeutic use
Biomarkers, Tumor
/ blood
Case-Control Studies
Circulating Tumor DNA
/ blood
Follow-Up Studies
High-Throughput Nucleotide Sequencing
Humans
Microsatellite Instability
Mutation
Neoplasms
/ blood
Prognosis
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Survival Rate
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
26
04
2019
revised:
17
05
2019
accepted:
07
08
2019
pubmed:
12
9
2019
medline:
22
9
2020
entrez:
12
9
2019
Statut:
ppublish
Résumé
Microsatellite instability (MSI) and high tumor mutation burden (TMB-High) are promising pan-tumor biomarkers used to select patients for treatment with immune checkpoint blockade; however, real-time sequencing of unresectable or metastatic solid tumors is often challenging. We report a noninvasive approach for detection of MSI and TMB-High in the circulation of patients. We developed an approach that utilized a hybrid-capture-based 98-kb pan-cancer gene panel, including targeted microsatellite regions. A multifactorial error correction method and a novel peak-finding algorithm were established to identify rare MSI frameshift alleles in cell-free DNA (cfDNA). Through analysis of cfDNA derived from a combination of healthy donors and patients with metastatic cancer, the error correction and peak-finding approaches produced a specificity of >99% ( These analyses demonstrate the feasibility of noninvasive pan-cancer screening and monitoring of patients who exhibit MSI or TMB-High and have a high likelihood of responding to immune checkpoint blockade.
Identifiants
pubmed: 31506389
pii: 1078-0432.CCR-19-1372
doi: 10.1158/1078-0432.CCR-19-1372
pmc: PMC6892397
mid: NIHMS1537534
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
Circulating Tumor DNA
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7024-7034Subventions
Organisme : NCI NIH HHS
ID : U10 CA180950
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103466
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA121113
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201600005C
Pays : United States
Organisme : NCI NIH HHS
ID : R43 CA217544
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM114737
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2019 American Association for Cancer Research.
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