RT Journal Article
T1 Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors.
A1 Serrano, César
A1 Vivancos, Ana
A1 López-Pousa, Antonio
A1 Matito, Judit
A1 Mancuso, Francesco M
A1 Valverde, Claudia
A1 Quiroga, Sergi
A1 Landolfi, Stefania
A1 Castro, Sandra
A1 Dopazo, Cristina
A1 Sebio, Ana
A1 Virgili, Anna C
A1 Menso, María M
A1 Martín-Broto, Javier
A1 Sansó, Miriam
A1 García-Valverde, Alfonso
A1 Rosell, Jordi
A1 Fletcher, Jonathan A
A1 George, Suzanne
A1 Carles, Joan
A1 Arribas, Joaquín
K1 Circulating tumor DNA
K1 Gastrointestinal stromal tumor
K1 Imatinib
K1 KIT
K1 Liquid biopsy
K1 PDGFRA
K1 Regorafenib
K1 Sarcoma
K1 Sunitinib
AB Gastrointestinal stromal tumor (GIST) initiation and evolution is commonly framed by KIT/PDGFRA oncogenic activation, and in later stages by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Thus, circulating tumor (ct)DNA determination is expected to be an informative non-invasive dynamic biomarker in GIST patients. We performed amplicon-based next-generation sequencing (NGS) across 60 clinically relevant genes in 37 plasma samples from 18 GIST patients collected prospectively. ctDNA alterations were compared with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) and cross-validated with droplet digital PCR (ddPCR). We were able to identify cfDNA mutations in five out of 18 patients had detectable in at least one timepoint. Overall, NGS sensitivity for detection of cell-free (cf)DNA mutations in plasma was 28.6%, showing high concordance with ddPCR confirmation. We found that GIST had relatively low ctDNA shedding, and mutations were at low allele frequencies. ctDNA was detected only in GIST patients with advanced disease after imatinib failure, predicting tumor dynamics in serial monitoring. KIT secondary mutations were the only mechanism of resistance found across 10 imatinib-resistant GIST patients progressing to sunitinib or regorafenib. ctDNA evaluation with amplicon-based NGS detects KIT primary and secondary mutations in metastatic GIST patients, particularly after imatinib progression. GIST exhibits low ctDNA shedding, but ctDNA monitoring, when positive, reflects tumor dynamics.
YR 2020
FD 2020-02-05
LK http://hdl.handle.net/10668/15051
UL http://hdl.handle.net/10668/15051
LA en
DS RISalud
RD Apr 11, 2025