Genotyping of Circulating Free DNA Enables Monitoring of Tumor Dynamics in Synovial Sarcomas.
circulating tumor DNA
ctDNA
diagnostic biomarker
liquid biopsy
next-generation sequencing
soft tissue sarcoma
synovial sarcoma
targeted sequencing
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
21 Apr 2022
21 Apr 2022
Historique:
received:
30
03
2022
revised:
18
04
2022
accepted:
19
04
2022
entrez:
14
5
2022
pubmed:
15
5
2022
medline:
15
5
2022
Statut:
epublish
Résumé
Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which lead to initiation and proliferation of tumor cells. The detection and quantification of circulating tumor DNA (ctDNA) can serve as a non-invasive method for diagnostics of local or distant tumor recurrence, which could improve survival rates due to early detection. We developed a subtype-specific targeted next-generation sequencing (NGS) approach specifically targeting SS t(X;18)(p11;q11), which fuses The subtype-specific assay allowed detection of somatic mutations from 25/25 tumors with a mean of 1.68 targetable mutations. The minimal limit of detection was determined at a variant allele frequency of 0.05%. Analysis of 29 plasma samples from 15 tumor patients identified breakpoint ctDNA in 6 patients (sensitivity: 40%, specificity 100%). The addition of more mutations further increased assay sensitivity. Quantification of ctDNA in plasma samples ( Targeted NGS allows for highly sensitive tumor profiling and non-invasive detection of ctDNA in SS patients, enabling non-invasive monitoring of tumor dynamics.
Sections du résumé
BACKGROUND
BACKGROUND
Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which lead to initiation and proliferation of tumor cells. The detection and quantification of circulating tumor DNA (ctDNA) can serve as a non-invasive method for diagnostics of local or distant tumor recurrence, which could improve survival rates due to early detection.
METHODS
METHODS
We developed a subtype-specific targeted next-generation sequencing (NGS) approach specifically targeting SS t(X;18)(p11;q11), which fuses
RESULTS
RESULTS
The subtype-specific assay allowed detection of somatic mutations from 25/25 tumors with a mean of 1.68 targetable mutations. The minimal limit of detection was determined at a variant allele frequency of 0.05%. Analysis of 29 plasma samples from 15 tumor patients identified breakpoint ctDNA in 6 patients (sensitivity: 40%, specificity 100%). The addition of more mutations further increased assay sensitivity. Quantification of ctDNA in plasma samples (
CONCLUSIONS
CONCLUSIONS
Targeted NGS allows for highly sensitive tumor profiling and non-invasive detection of ctDNA in SS patients, enabling non-invasive monitoring of tumor dynamics.
Identifiants
pubmed: 35565213
pii: cancers14092078
doi: 10.3390/cancers14092078
pmc: PMC9105697
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Oncogene. 2003 Apr 10;22(14):2215-22
pubmed: 12687023
Am J Pathol. 2001 Dec;159(6):2117-24
pubmed: 11733362
Am J Surg Pathol. 2001 Mar;25(3):406-10
pubmed: 11224613
Oncotarget. 2015 May 20;6(14):12234-47
pubmed: 25906748
Hum Mol Genet. 1995 Jun;4(6):1097-9
pubmed: 7655467
Mol Cancer. 2015 Aug 07;14:151
pubmed: 26250552
Mol Cancer Res. 2006 Jul;4(7):499-510
pubmed: 16849525
Mol Cancer. 2022 Feb 14;21(1):50
pubmed: 35164780
J Pediatr Hematol Oncol. 2022 Feb 09;:
pubmed: 35137727
Cell. 2013 Mar 28;153(1):71-85
pubmed: 23540691
Br J Cancer. 2014 May 13;110(10):2420-6
pubmed: 24736584
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Nat Genet. 1994 Aug;7(4):502-8
pubmed: 7951320
Stem Cells Int. 2016;2016:6146047
pubmed: 27069481
Int J Surg Pathol. 2022 Jun;30(4):360-369
pubmed: 34866460
Cancer Sci. 2012 Sep;103(9):1625-30
pubmed: 22726592
Mod Pathol. 2000 Sep;13(9):994-1004
pubmed: 11007040
Int J Cancer. 2019 Aug 15;145(4):1148-1161
pubmed: 30779112
J Biol Chem. 2010 Dec 3;285(49):38093-103
pubmed: 20929863
Oncotarget. 2015 Oct 27;6(33):34680-90
pubmed: 26415226
Blood. 2018 Feb 1;131(5):496-504
pubmed: 29141946
J Biol Chem. 2015 Jul 10;290(28):17462-73
pubmed: 26023234
Clin Cancer Res. 2021 Nov 1;27(21):5922-5930
pubmed: 34426444
J Clin Oncol. 2021 Dec 10;39(35):3927-3937
pubmed: 34623899
Nat Methods. 2015 May;12(5):423-5
pubmed: 25849638
Ann Oncol. 2021 Nov;32(11):1348-1365
pubmed: 34303806
J Surg Oncol. 2008 Mar 15;97(4):314-20
pubmed: 18286474
Nat Med. 2008 Sep;14(9):985-90
pubmed: 18670422
Lab Invest. 1992 Oct;67(4):498-505
pubmed: 1331610
Sci Rep. 2017 Nov 7;7(1):14634
pubmed: 29116117
Oncogene. 2012 Oct 4;31(40):4384-96
pubmed: 22231445
J Cancer Res Clin Oncol. 2021 Dec;147(12):3735-3747
pubmed: 34272609
Clin Orthop Relat Res. 2014 Mar;472(3):874-82
pubmed: 23716114