Longitudinal Copy-Number Alteration Analysis in Plasma Cell-Free DNA of Neuroendocrine Neoplasms is a Novel Specific Biomarker for Diagnosis, Prognosis, and Follow-up.

Autor:	Boons G; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium., Vandamme T; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp, Belgium. Timon.Vandamme@uantwerpen.be.; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium.; NETwerk, Antwerp University Hospital, Edegem, Belgium., Mariën L; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium., Lybaert W; NETwerk, Antwerp University Hospital, Edegem, Belgium.; Department of Medical Oncology, AZ Nikolaas, Sint-Niklaas, Belgium., Roeyen G; NETwerk, Antwerp University Hospital, Edegem, Belgium.; Department of Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium., Rondou T; NETwerk, Antwerp University Hospital, Edegem, Belgium.; Department of Gastroenterology, AZ Rivierenland, Bornem, Belgium., Papadimitriou K; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Janssens K; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium., Op de Beeck B; NETwerk, Antwerp University Hospital, Edegem, Belgium.; Department of Radiology, Antwerp University Hospital, Edegem, Belgium., Simoens M; NETwerk, Antwerp University Hospital, Edegem, Belgium.; Department of Gastroenterology, Ziekenhuis Netwerk Antwerpen, Antwerp, Belgium., Demey W; NETwerk, Antwerp University Hospital, Edegem, Belgium.; Department of Medical Oncology, AZ Klina, Brasschaat, Belgium.; Department of Oncology, AZ Voorkempen, Malle, Belgium., Dero I; NETwerk, Antwerp University Hospital, Edegem, Belgium.; Department of Gastroenterology, Gasthuiszusters Antwerpen, Antwerp, Belgium., Van Camp G; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium., Peeters M; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.; NETwerk, Antwerp University Hospital, Edegem, Belgium., Op de Beeck K; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Jan 15; Vol. 28 (2), pp. 338-349. Date of Electronic Publication: 2021 Nov 10.
DOI:	10.1158/1078-0432.CCR-21-2291
Abstrakt:	Purpose: As noninvasive biomarkers are an important unmet need for neuroendocrine neoplasms (NEN), biomarker potential of genome-wide molecular profiling of plasma cell-free DNA (cfDNA) was prospectively studied in patients with NEN. Experimental Design: Longitudinal plasma samples were collected from patients with well-differentiated, metastatic gastroenteropancreatic and lung NEN. cfDNA was subjected to shallow whole-genome sequencing to detect genome-wide copy-number alterations (CNA) and estimate circulating tumor DNA (ctDNA) fraction, and correlated to clinicopathologic and survival data. To differentiate pancreatic NENs (PNEN) from pancreatic adenocarcinomas (PAAD) using liquid biopsies, a classification model was trained using tissue-based CNAs and validated in cfDNA. Results: One hundred and ninety-five cfDNA samples from 43 patients with NEN were compared with healthy control cfDNA ( N = 100). Plasma samples from patients with PNEN ( N = 21) were used for comparison with publicly available PNEN tissue ( N = 98), PAAD tissue ( N = 109), and PAAD cfDNA ( N = 96). Thirty percent of the NEN cfDNA samples contained ctDNA and 44% of the patients had at least one ctDNA-positive (ctDNA + ) sample. CNAs detected in cfDNA were highly specific for NENs and the classification model could distinguish PAAD and PNEN cfDNA samples with a sensitivity, specificity, and AUC of 62%, 86%, and 79%, respectively. ctDNA-positivity was associated with higher World Health Organization (WHO) grade, primary tumor location, and higher chromogranin A and neuron-specific enolase values. Overall survival was significantly worse for ctDNA + patients and increased ctDNA fractions were associated with poorer progression-free survival. Conclusions: Sequential genome-wide profiling of plasma cfDNA is a novel, noninvasive biomarker with high specificity for diagnosis, prognosis, and follow-up in metastatic NENs. (©2021 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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