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Article Dans Une Revue Clinical Cancer Research Année : 2012

Pyrophosphorolysis-Activated Polymerization Detects Circulating Tumor DNA in Metastatic Uveal Melanoma

Jordan Madic
  • Fonction : Auteur
Sophie Piperno-Neumann
  • Fonction : Auteur
Vincent Servois
  • Fonction : Auteur
Aurore Rampanou
  • Fonction : Auteur
Maud Milder
  • Fonction : Auteur
David Gentien
  • Fonction : Auteur
Stéphanie Saada
  • Fonction : Auteur
Franck Assayag
  • Fonction : Auteur
Aurélie Thuleau
  • Fonction : Auteur
Fariba Nemati
  • Fonction : Auteur
Didier Decaudin
  • Fonction : Auteur
François-Clément Bidard
  • Fonction : Auteur
Laurence Desjardins
  • Fonction : Auteur
Pascale Mariani
  • Fonction : Auteur
Olivier Lantz
  • Fonction : Auteur
Marc-Henri Stern
  • Fonction : Auteur

Résumé

Abstract Purpose: To develop a molecular tool to detect circulating tumor–derived DNA (ctDNA) in the plasma from patients with uveal melanoma as a marker of tumor burden and monitor treatment efficacy. Experimental Design: A real-time PCR was developed on the basis of bidirectional pyrophosphorolysis-activated polymerization (bi-PAP) for the quantification of ctDNA using 3′blocked primer pairs specific for the 3 recurrent mutually exclusive mutations of Gα subunits GNAQ and GNA11. Results: Sensitivity and specificity of bi-PAP were assessed on serial dilutions of tumor DNA in normal DNA for the 3 recurrent mutations. Each assay could detect a single mutated molecule per reaction, whereas 104 copies of normal DNA were not detected. The ctDNA was readily detected in plasma of mice bearing uveal melanoma xenografts in amounts proportional to circulating human DNA. Finally, plasma was almost always found positive (20 of 21 tested patients) in a prospective analysis of patients with metastatic uveal melanoma. Conclusions: Bi-PAP assays detect and quantify ctDNA in patients with metastatic uveal melanoma. A prospective study is ongoing to assess the clinical usefulness of ctDNA level in uveal melanoma. Clin Cancer Res; 18(14); 3934–41. ©2012 AACR.

Dates et versions

hal-04409149 , version 1 (22-01-2024)

Identifiants

Citer

Jordan Madic, Sophie Piperno-Neumann, Vincent Servois, Aurore Rampanou, Maud Milder, et al.. Pyrophosphorolysis-Activated Polymerization Detects Circulating Tumor DNA in Metastatic Uveal Melanoma. Clinical Cancer Research, 2012, 18 (14), pp.3934-3941. ⟨10.1158/1078-0432.CCR-12-0309⟩. ⟨hal-04409149⟩

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