Multidisciplinary research presents new protocol for the functional characterization of missense type mutations in the gene coding for the adhesion molecule E-cadherin.

Authors and Affiliations:

Soraia Melo ^1,2,3, Joana Figueiredo ^1,2, Maria Sofia Fernandes ^1,2,4, Margarida Gonçalves ^1,5, Eurico Morais-de-Sá ^1,5, João Miguel Sanches ⁴ and Raquel Seruca ^1,2,3

¹ Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal

² Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), 4200-135 Porto, Portugal

³ Medical Faculty, University of Porto, 4200-135 Porto, Portugal

⁴ Institute for Systems and Robotics (ISR), Instituto Superior Técnico (IST), 1049-001 Lisboa, Portugal

⁵ Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal

Abstract:

The role of E-cadherin in Hereditary Diffuse Gastric Cancer (HDGC) is unequivocal. Germline alterations in its encoding gene (CDH1) are causative of HDGC and occur in about 40% of patients. Importantly, while in most cases CDH1 alterations result in the complete loss of E-cadherin associated with a well-established clinical impact, in about 20% of cases the mutations are of the missense type. The latter are of particular concern in terms of genetic counselling and clinical management, as the effect of the sequence variants in E-cadherin function is not predictable. If a deleterious variant is identified, prophylactic surgery could be recommended. Therefore, over the last few years, intensive research has focused on evaluating the functional consequences of CDH1 missense variants and in assessing E-cadherin pathogenicity. In that context, our group has contributed to better characterize CDH1 germline missense variants and is now considered a worldwide reference centre. In this review, we highlight the state of the art methodologies to categorize CDH1 variants, as neutral or deleterious. This information is subsequently integrated with clinical data for genetic counseling and management of CDH1 variant carriers.

Journal: International Journal of Molecular Sciences (nt. J. Mol. Sci.)

Link: http://www.mdpi.com/1422-0067/18/12/2687