Comparative targeted genome profiling between solid and liquid biopsies in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a proof-of-concept pilot study.

Clinical presentation and genetic profile of gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are highly variable, hampering their management. Sequencing of circulating tumor DNA (ctDNA) from liquid biopsy (LB) has been proposed as a less invasive alternative to solid biopsy (SB). Our aim is to compare the mutational profile (MP) provided by LB with that deriving from SB in GEP-NETs. SB and LB derived simultaneously from 6 GEP-NETs patients. A comparative targeted Next Generation Sequencing (NGS) analysis was performed on DNA from SB and LB to evaluate the mutational status of 11 genes (MEN1, DAXX, ATRX, MUTYH, SETD2, DEPDC5, TSC2, ARID1A, CHECK2, MTOR, PTEN). Patients (M:F =2:1; median age 64 yrs) included 3 with pancreatic and 3 with ileal NETs. NGS detected a median number of 55 variants/sample in SB and 66.5 variants/sample in LB specimens (mutational burden: 0.2-1.9 and 0.3-1.8 mut/Mb, respectively). Missense and nonsense mutations were prevalent in both, mainly represented by C>T transitions. ARID1A, MTOR, and ATRX were consistently mutated in SB and ARID1A, TSC2, MEN1, PTEN, SETD2, and MUTYH were consistently mutated in LB. DAXX mutations were absent in LB. 17 recurrent mutations were shared between SB and LB; in particular, MTOR single nucleotide variants (SNVs) c.G4731A and c.C2997T were shared by 5 out of 6 patients. Hierarchical clustering supported genetic similarity between SB and LB. This pilot study explores the applicability of LB in GEP-NETs MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.

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The Author(s). Published by S. Karger AG, Basel.