Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes: Diagnostic performance in the Hereditary Cancer Programme of the Valencia Community (FamCan-NGS)

Marta Ramírez-Calvo, Zaida García-Casado, Antonio Fernández-Serra, Inmaculada De Juan, Sarai Palanca, Silvestre Oltra, José Luis Soto, Adela Castillejo, Víctor M. Barbera, Ma José Juan-Fita, Ángel Segura, Isabel Chirivella, Ana Beatriz Sánchez, Isabel Tena, Carolina Chaparro, Dolores Salas, José Antonio López-Guerrero

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Approximately 5 to 10% of all cancers are caused by inherited germline mutations, many of which are associated with different Hereditary Cancer Syndromes (HCS). In the context of the Program of Hereditary Cancer of the Valencia Community, individuals belonging to specific HCS and their families receive genetic counselling and genetic testing according to internationally established guidelines. The current diagnostic approach is based on sequencing a few high-risk genes related to each HCS; however, this method is time-consuming, expensive and does not achieve a confirmatory genetic diagnosis in many cases. This study aims to test the level of improvement offered by a Next Generation Sequencing (NGS) gene-panel compared to the standard approach in a diagnostic reference laboratory setting. Methods: A multi-gene NGS panel was used to test a total of 91 probands, previously classified as non-informative by analysing the high-risk genes defined in our guidelines. Results: Nineteen deleterious mutations were detected in 16% of patients, some mutations were found in already-tested high-risk genes (BRCA1, BRCA2, MSH2) and others in non-prevalent genes (RAD51D, PALB2, ATM, TP53, MUTYH, BRIP1). Conclusions: Overall, our findings reclassify several index cases into different HCS, and change the mutational status of 14 cases from non-informative to gene mutation carriers. In conclusion, we highlight the necessity of incorporating validated multi-gene NGS panels into the HCSs diagnostic routine to increase the performance of genetic diagnosis.

Original languageEnglish
Article number3
JournalHereditary Cancer in Clinical Practice
Volume17
Issue number1
DOIs
StatePublished - 18 Jan 2019

Bibliographical note

Publisher Copyright:
© 2019 The Author(s).

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Diagnostic accuracy
  • Genetic counselling
  • Hereditary Cancer syndrome
  • Multi-gene panel
  • Next generation sequencing

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