Proof of concept: prognostic value of the plasmatic concentration of circulating cell free DNA in desmoid tumors using ddPCR

// Nicolas Macagno 1, 2, * , Frederic Fina 1, 3, * , Nicolas Penel 4 , Corinne Bouvier 1, 2 , Isabelle Nanni 5 , Florence Duffaud 6, 7 , Raquel Rouah 5 , Bruno Lacarelle 8 , L'houcine Ouafik 5 , Sylvie Bonvalot 9 and Sebastien Salas 6, 7 1 Department of Pathology, Assistance Publique Hopitaux de Marseille Timone Hospital, Marseille, France 2 Aix-Marseille University, Medical Faculty, CRO2, UMR 911 (Equipe IV), Marseille, France 3 ID-Solutions, Grabels, France 4 Department of General Oncology, Oscar Lambret Center, Lille, France 5 Department of Molecular Oncology, Assistance Publique Hopitaux de Marseille, Marseille, France 6 Department of Oncology, Assistance Publique Hopitaux de Marseille Timone Hospital, Marseille, France 7 Aix-Marseille University, Medical Faculty, Marseille, France 8 Department of Medical Biology, Assistance Publique Hopitaux de Marseille Timone Hospital, Marseille, France 9 Department of Surgery, Institut Curie, PSL Univeristy, Paris, France * These authors contributed equally to this work Correspondence to: Sebastien Salas, email: sebastien.salas@ap-hm.fr Keywords: ddPCR; cfDNA; CTNNB1; desmoid; prognosis Received: October 27, 2017 Accepted: February 25, 2018 Published: April 06, 2018 ABSTRACT Since desmoid tumors (DT) exhibit an unpredictable clinical course, with stabilization and/or spontaneous regression, an initial “wait-and-see” policy is the new standard of care–thus, the actual challenge is to identify early factors of progression. We present a method of detection of CTNNB1 mutations using a targeted digital droplet PCR (ddPCR) on cell-free DNA (cfDNA) extracted from blood samples of 31 DT patients. Furthermore, we analyzed the correlation between DT evolution and plasmatic concentration of total and mutated cfDNA at the time of diagnosis. Circulating copies of CTNNB1 mutants (ctDNA) were detected in the plasma of 6 patients (33%) but their concentration was not correlated with evolution of the tumor. Concentration of total cfDNA was higher in the plasma of patients with progressive desmoids ( p = 0,0009). Using a threshold 1375, it was possible to predict desmoid evolution for 65% of patients by measuring the quantity of circulating DNA in their plasma as early as the time of diagnosis. Albeit showing that the detection of CTNNB1 mutants is possible in the plasma of patients harboring a desmoid tumor, the results of this preliminary study raise the hypothesis that most of the circulating DNA detected in their plasma is derived from non-neoplastic cells, most likely normal neighboring tissues being actively invaded. Our results open the perspective of using cfDNA as a biomarker to predict prognosis at the time of diagnosis and assess tumor dynamics to optimize the treatment strategy.