Cdh1, encoding E-cadherin, is a crucial gene. E-cadherin is a key protein in adherens junctions, involved in major cellular processes like embryogenesis and maintaining tissue architecture. It is recognized as a tumour suppressor gene, and its loss of function has deleterious effects. CDH1-related pathways are associated with the development and maintenance of normal tissue structure, and genetic models are valuable for studying its functions [5].

Pathogenic CDH1 germline mutations are associated with lobular breast cancer in the hereditary lobular breast cancer (HLBC) syndrome, and may also be related to the hereditary diffuse gastric cancer (HDGC) syndrome. In families with the HDGC syndrome, CDH1 splicing and missense germline mutations occur more frequently in healthy subjects than in patients with gastric cancer, suggesting not all pathogenic mutations confer the same cancer-developing risk [1,3]. Women with germline CDH1 variants and diffuse gastric cancer are relatively common in the HDGC syndrome, especially young women potentially at higher risk [4]. Also, in women with the HLBC phenotype, P/LP germline CDH1 variants were identified in some cases, and an inactivating CDH1 mechanism was found in some matched tumor samples of these carriers. These variants may provide a new way to test women with early-onset lobular breast cancer and/or positive family history of breast cancer [2].

In conclusion, Cdh1 is essential for maintaining tissue architecture and has a critical tumour-suppressing function. Studies on CDH1 germline mutations in mouse models and human subjects contribute to understanding its role in diseases like lobular breast cancer and diffuse gastric cancer, which can potentially guide prophylactic and screening procedures for related cancer-prone populations [1,2,3,4,5].

References:

1. Girardi, Antonia, Magnoni, Francesca, Vicini, Elisa, Veronesi, Paolo, Corso, Giovanni. . CDH1 germline mutations in families with hereditary lobular breast cancer. In European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 31, 274-278. doi:10.1097/CEJ.0000000000000688. https://pubmed.ncbi.nlm.nih.gov/33990097/

2. Corso, Giovanni, Marino, Elena, Zanzottera, Cristina, Bonanni, Bernardo, Veronesi, Paolo. 2024. CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype. In JAMA network open, 7, e247862. doi:10.1001/jamanetworkopen.2024.7862. https://pubmed.ncbi.nlm.nih.gov/38652475/

3. Corso, Giovanni, Magnoni, Francesca, Massari, Giulia, Galimberti, Viviana, Bagnardi, Vincenzo. 2021. CDH1 germline mutations in healthy individuals from families with the hereditary diffuse gastric cancer syndrome. In Journal of medical genetics, 59, 313-317. doi:10.1136/jmedgenet-2021-108226. https://pubmed.ncbi.nlm.nih.gov/34952833/

4. Corso, Giovanni, Comelli, Giovanni, Veronesi, Paolo, Bagnardi, Vincenzo, Magnoni, Francesca. 2023. Germline CDH1 variants in hereditary diffuse gastric cancer syndrome with focus on younger women. In Journal of cancer research and clinical oncology, 149, 16147-16155. doi:10.1007/s00432-023-05318-5. https://pubmed.ncbi.nlm.nih.gov/37639007/

5. Figueiredo, Joana, Melo, Soraia, Carneiro, Patrícia, Paredes, Joana, Seruca, Raquel. 2019. Clinical spectrum and pleiotropic nature of CDH1 germline mutations. In Journal of medical genetics, 56, 199-208. doi:10.1136/jmedgenet-2018-105807. https://pubmed.ncbi.nlm.nih.gov/30661051/