CDH1 - Sept 2018

Project title:
CDH1 Variant Database: an essential tool for genotype-phenotype studies in CDH1 germline Carriers

Project leader:
Carla Oliveira; Instituto de Investigação e Inovação em Saúde, Porto University, Portugal / P.CCCC - Porto.Comprehensive Cancer Centre, Porto, Portugal

Project Description:
Hereditary Diffuse Gastric Cancer (HDGC) is an autosomal dominant cancer syndrome that predisposes for diffuse gastric cancer (DGC) and/or lobular breast cancer (LBC). HDGC is mainly caused by CDH1 inactivating single nucleotide variants (SNVs). Germline CDH1 copy number variants (CNVs) and CTNNA1 truncating variants have also been described to cause HDGC. Pathogenic and likely pathogenic CDH1 variants, classified according to CDH1 ACMG variant curation guidelines are actionable and trigger a clinical pathway of care involving surveillance and prophylaxis in asymptomatic carriers. A large number of individuals and families, both fulfilling or not the clinical criteria of HDGC, also present with variants of unknown significance (VUS), which are difficult to manage clinically, mainly due to a lack of robust clinical data.

In this project, we systematically identified individuals and families bearing rare CDH1 germline variants with or without HDGC criteria and classified the respective variants according to the specific CDH1 ACMG variant curation guidelines. Further, we collected clinical information from probands and relatives to generate bonafide genotype-phenotype associations.

No identification of patients, families or clinical records were necessary.

These data were collected in a CDH1 germline database and both GENTURIS and non-GENTURIS members were welcome to participate.

Collaborators in this study were welcome to join as authors in scientific public presentations or publications, and were always acknowledged for their involvement in the study.

12 ERN GENTURIS centers and 3 Supporting Partners from the UK participated in this study.

Start date: September 2018

Duration: 5 years

Funder: SolveRD PhD Studentship to José Pelaez