CTNNA1 - Oct 2021

Project title:
CTNNA1 Variant Database: an essential tool for genotype-phenotype studies in CTNNA1 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 and copy number variants and, recently, it was discovered that CTNNA1 truncating single nucleotide variants also cause HDGC. CTNNA1 is a recent HDGC-associated gene, that encodes for α-E-catenin, a protein that associates with the cytoplasmic domain of classical cadherins, forming the adherens junction complex. CTNNA1 missense germline variants are known to also cause patterned macular dystrophy-2, and several potentially truncating CTNNA1 variants have been found associated with other cancer types besides diffuse gastric cancer.

In this project, we wish to systematically identify individuals and families bearing rare CTNNA1 germline variants with or without HDGC criteria, classify the respective variants according to the specific CDH1 ACMG variant curation guidelines. Further, we wish to collect clinical information from probands and relatives to generate bonafide genotype-phenotype associations.

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

These data will be collected in a CTNNA1 germline database and both GENTURIS and non-GENTURIS members are welcome to participate.

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

5 ERN GENTURIS centres have contributed already.

Start date: October 2021

Duration: 3 years

Funder: The Portuguese Foundation for Science and Technology (FCT) PhD Studentship reference 2020.05773.BD