TY - JOUR

T1 - Pre-and Postoperative Circulating Tumour DNA in Patients with Gastrointestinal Stromal Tumour

T2 - A Methodological Assessment Study

AU - Brinch, Charlotte Margareta

AU - Aggerholm-Pedersen, Ninna

AU - Poulsen, Tim Svenstrup

AU - Skovrider-Ruminski, Wojciech

AU - de Heer, Pieter

AU - Penninga, Luit

AU - Krarup-Hansen, Anders

AU - Hogdall, Estrid

N1 - Funding Information: Candys Foundation (grant number 2019-332), the Fund for the Promotion of Medical Science (grant number 18-L-0161), Harboe Foundation (grant number 18250), Herlev & Gentofte’s Research Council, Beckett Foundation (grant number 19-2-3833), Agnes and Poul Friis Foundation (grant number 81008-003), Else and Mogens Wedells Foundation (grant number 11-20-1), Aase and Ejnar Danielsen’s Foundation (grant number 20-10-0045), and Toemrermester Joergen Holm and hustru Elisa f. Hansens Memorial Scholarship (grant number 20010) funded this research.

PY - 2022

Y1 - 2022

N2 - Background/Aim: Gastrointestinal stromal tumours (GISTs) harbour genetic aberrations in receptor tyrosine kinase KIT (KIT) or platelet-derived growth factor receptor A (PDGFRA) in 85-90% of the patients. Circulating tumour DNA (ctDNA) is a potential biomarker in patients with GIST. Previous studies investigating ctDNA around surgery in patients with GIST presented divergent results regarding the proportion of patients with detectable ctDNA. This study aimed to 1) investigate the feasibility of detecting and monitoring ctDNA pre-and postoperative, 2) compare two different circulating free DNA (cfDNA) extraction methods, and validate results obtained by next-generation sequencing (NGS) using Real-Time PCR technology. Patients and Methods: Eight patients planned for immediate surgery or surgery after neoadjuvant oncological treatment were included in the study, from whom blood collection was performed pre- and postoperatively for ctDNA analysis. Furthermore, blood samples from six patients with GIST harbouring a point mutation in KIT or PDGFRA in tissues from primary tumours were used for comparison and validation sub-study. Results: In this explorative study, none of the patients with very low to intermediate risk GIST harboured KIT, or PDGFRA mutated ctDNA in pre-or postoperative blood samples. The methods used for cfDNA extraction gave similar output, and the two methods for ctDNA analysis gave identical results. Conclusion: There is no benefit in analysing ctDNA around surgery in very low to intermediate-risk GIST patients. Larger studies investigating ctDNA in patients with high-risk GIST around surgery are warranted.

AB - Background/Aim: Gastrointestinal stromal tumours (GISTs) harbour genetic aberrations in receptor tyrosine kinase KIT (KIT) or platelet-derived growth factor receptor A (PDGFRA) in 85-90% of the patients. Circulating tumour DNA (ctDNA) is a potential biomarker in patients with GIST. Previous studies investigating ctDNA around surgery in patients with GIST presented divergent results regarding the proportion of patients with detectable ctDNA. This study aimed to 1) investigate the feasibility of detecting and monitoring ctDNA pre-and postoperative, 2) compare two different circulating free DNA (cfDNA) extraction methods, and validate results obtained by next-generation sequencing (NGS) using Real-Time PCR technology. Patients and Methods: Eight patients planned for immediate surgery or surgery after neoadjuvant oncological treatment were included in the study, from whom blood collection was performed pre- and postoperatively for ctDNA analysis. Furthermore, blood samples from six patients with GIST harbouring a point mutation in KIT or PDGFRA in tissues from primary tumours were used for comparison and validation sub-study. Results: In this explorative study, none of the patients with very low to intermediate risk GIST harboured KIT, or PDGFRA mutated ctDNA in pre-or postoperative blood samples. The methods used for cfDNA extraction gave similar output, and the two methods for ctDNA analysis gave identical results. Conclusion: There is no benefit in analysing ctDNA around surgery in very low to intermediate-risk GIST patients. Larger studies investigating ctDNA in patients with high-risk GIST around surgery are warranted.

KW - circulating tumour DNA

KW - Gastrointestinal stromal tumour

KW - next-generation sequencing

U2 - 10.21873/anticanres.16022

DO - 10.21873/anticanres.16022

M3 - Journal article

C2 - 36288871

AN - SCOPUS:85140808706

VL - 42

SP - 5527

EP - 5537

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 11

ER -