Detection of tumor ALK status in neuroblastoma patients using peripheral blood

Cancer Medicine

Valérie Combaret³  Isabelle Iacono³  Angela Bellini⁵  Stéphanie Bréjon³  Virginie Bernard¹  Aurélien Marabelle⁶  Carole Coze²  Gaelle Pierron⁴  Eve Lapouble⁴  Gudrun Schleiermacher⁵ 

[1] Plateforme de séquençage ICGEX, Institut Curie, Paris Cedex 05, France;Aix-Marseille University et APHM, Hôpital d'Enfants de La Timone, Service d'Hématologie-Oncologie Pédiatrique, Marseille Cedex 05, France;Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon Cedex 08, France;Institut Curie, Unité de Génétique Somatique, Paris Cedex 05, France;INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Equipe Recherche Translationnelle en Oncologie Pédiatrique et Département d'Oncologie Pédiatrique, Institut Curie, Paris Cedex 05, France;Centre Léon-Bérard, Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon Cedex 08, France

关键词: ALK mutation;    cell‐free DNA;    ddPCR;    neuroblastoma;   

DOI  :  10.1002/cam4.414

来源: Wiley

【 摘 要 】

Abstract

New protocols based on ALK-targeted therapy by crizotinib or other ALK-targeting molecules have opened for the treatment of patients with neuroblastoma (NB) if their tumors showed mutation and/or amplification of the ALK gene. However, tumor samples are not always available for analysis of ALK mutational status in particular at relapse. Here, we evaluated the ALK mutational status of NB samples by analysis of circulating DNA, using the droplet digital PCR (ddPCR) system. ddPCR assays was developed for the detection of ALK mutations at F1174 and R1275 hotspots found in NB tumors and was applied for the analysis of circulating DNA obtained from 200 μL of serum or plasma samples collected from 114 patients with NB. The mutations F1174L (exon 23 position 3520, T>C and position 3522, C>A) and the mutation R1275Q (exon 25 position 3824, G>A) were detected in circulating DNA. The sensitivity of our test was 100%, 85%, and 92%, respectively, and the specificity was 100%, 91%, and 98%, respectively. In conclusion, the assay that we have developed offers a reliable, noninvasive blood test to assess ALK mutational status at F1174 and R1275 hotspots and should help clinicians to identify patients showing an ALK mutation in particular when no tumor tissue is available.

【 授权许可】

CC BY   
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.