Gene-panel sequencing spurs improved diagnosis of hereditary cancer

  • Between 50 – 75% of the most common hereditary cancers (breast and colon) escape the diagnostic ´lens´ when only factoring in the most frequent cancer-causing genes including BRCA1, BRCA2, as well as those implicated in Lynch syndrome.
  • The use of simultaneous multiple gene analysis techniques, thanks to next generation sequencing, has facilitated the molecular diagnosis of a group of patients that evaded traditional diagnostic identification techniques
  • Gene-panel sequencing enters the clinic for the diagnosis of hereditary cancer and the Vall d´Hebron Institute of Oncology (VHIO)-Vall d´Hebron University Hospital (HUVH), and the Catalan Institute of Oncology (ICO) are the first two centers in Spain to present results for the diagnosis of familial susceptibility to cancer

Barcelona, 02 November 2015.– The Vall d´Hebron Institute of Oncology (VHIO)-Vall d´Hebron University Hospital (HUVH) and the Catalan Institute of Oncology (ICO), last Thursday presented pioneering studies in Spain evidencing the clinical application of gene-panels in hereditary cancer.

Showcased during the annual meeting of the Sociedad Española de Oncología Médica (SEOM – the Spanish Society of Medical Oncology), ICO´s research centered on comparing two multiplex gene panels – one of which was their own design – and the study of the whole exome in order to validate its analytical validity in diagnosing hereditary cancer. The VHIO-HUVH revealed preliminary results from their own gene panel in a group of families with hereditary breast and ovarian cancers without identified mutations in BRCA genes to evidence effectiveness at clinical level.

Only 25% of families with hereditary breast/ovarian cancer are detected through the analysis of BRCA1 and BRCA2. It is therefore a critical need to develop new tools to genetically diagnose the remaining 75% of cases. The answer can be found in many other susceptibility genes, but the analysis can only be carried out through next generation sequencing – one of the most important technological advances in the diagnosis and characterization of cancer over recent years.

A multidisciplinary team comprised of VHIO´s Oncogenetics and High Risk & Cancer Prevention groups – both affiliated to HUVH as well as the Universidad Autónoma de Barcelona, analysed 200 BRCA1/2-negative families using a panel of 98 genes associated with hereditary breast/ovarian cancer. This study has led to the molecular diagnosis of a group of these patients, which has in turn influenced the medical management of these individuals and their families, as well as opening up better outcomes at clinical level. These initial findings including the study of 119 patients who underwent multiple gene analysis, were reported thanks to the diagnostic panels which are being evaluated at VHIO in collaboration with the HUVH´s Medical Oncology Service and Genetics and Clinical and Molecular Genetics Departments.

The research led by the VHIO-HUVH team, presented by Irene Esteban, Genetic Counselor of the group, has led to the additional genetic diagnosis of 1 in every 6 women following a BRCA1 and BRCA2-negative result. Among the genes under study, PTEN, PALB2, RAD51D, PMS2, BRIP1 stand out in particular, and the identification of mutations in these genes has led to a modification in the recommendations for early prevention and detection in these patients and their families.

“This additional diagnosis represents an important forward step in the field of cancer prevention since it provides us with useful information to better personalize recommendations for monitoring and prevention”, explains Judith Balmaña, Principal Investigator of VHIO´s High Risk & Prevention Group, and co-coordinator of the study along with Orland Díez, Principal Investigator of VHIO´s Oncogenetics Group.

The conclusion of their findings is that the simultaneous analysis of high-penetrance gene panels is a proven, clinically relevant tool for genetic diagnosis in patients with hereditary breast and ovarian cancer. Furthermore, “it involves the identification of gene variants with moderate penetrance and variants of unknown significance, which remain an important focus of clinical research”, says Orland Díez. It can no longer be said that there is only one breast cancer or ovarian cancer gene, rather, that there are multiple breast or ovarian cancer predisposing genes.

The study presented by ICO´s Hereditary Cancer Program was carried out in collaboration with the Institute of Predictive and Personalized Medicine of Cancer (IMPPC) and the Centro Nacional de Análisis Genómicos (CNAG – National Center of Genomic Anlyses). ICO´s Conxi Lázaro, co-coordinator of the research, observes “the importance of validating these methodologies prior to their routine use for diagnosis is crucial”. The results, delivered by Joan Brunet in the same oral presentation session at the SEOM Congress, indicate that “Compared to traditional approaches, the use of gene panels represents an advance in the genetic diagnosis of hereditary cancer. We can now identify new mutations in families with suspected hereditary cancer that would have evaded detection using the same methodology employed up until now”.

In order to validate the utility of the gene-panel research focused on a group of 20 cases with a known mutation. They also studied 14 cases with no previously detected mutation in the most common genes. Concerning the latter, the application of gene panels led to the identification of new mutations in 50% of families. The study involved the collaboration of many professionals from several different disciplines and the participating families were from among the 3 genetic counseling units across ICO´s research centers.

According to the coordinators of both studies presented during SEOM´s Congress, these findings evidence “the necessity of incorporating these panels for multiple gene analysis in the diagnosis of hereditary cancer. We believe that the broadened genetic study of predisposition to cancer represents an important advance with exponential benefits in the prevention of cancer”, conclude the experts.


For more information: Amanda Wren • Director of Communications, the Vall d’Hebron Institute of Oncology (VHIO) • Tel. +34 695 207 886

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