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Whereas HDGC is associated with\n                    <jats:italic>CDH1<\/jats:italic>\n                    and\n                    <jats:italic>CTNNA1<\/jats:italic>\n                    variants and defined by an increased risk of diffuse gastric cancer and lobular breast cancer, Lynch syndrome results from alterations in mismatch repair genes, whose main manifestations include colorectal, endometrial, ovarian, breast, prostate, stomach, and urological tumours. Remarkably, a huge difference remains in the knowledge surrounding the molecular mechanisms that drive these disorders, and in current approaches for patient management. In fact, the HDGC narrative is still in its early stages when compared with Lynch syndrome, which accumulates more than a century of research. Herein, we propose an analogy between HDGC and Lynch syndromes, highlighting intricacies across genetic origin, variant effects, cellular landscapes, and associated clinical outcomes. Further, we postulate that the history of Lynch syndrome may be useful to advance HDGC aetiology, namely strategies for identification of new candidate genes, rules for variant interpretation, sources of phenotypic heterogeneity, and improved surveillance protocols. This collected data will impact clinical perspectives, as well as future research programs addressing HDGC unmet challenges.\n                  <\/jats:p>","DOI":"10.1038\/s41431-025-01992-w","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T14:46:14Z","timestamp":1766414774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hereditary diffuse gastric cancer in progress: Comparative lessons from Lynch syndrome"],"prefix":"10.1038","author":[{"given":"Joana","family":"Pereira","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-7487","authenticated-orcid":false,"given":"Lu\u00edsa","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Soraia","family":"Melo","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcia","family":"Carneiro","sequence":"additional","affiliation":[]},{"given":"Maria Sofia","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Raquel","family":"Seruca","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-1974","authenticated-orcid":false,"given":"Joana","family":"Figueiredo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Okur V, Chung WK: The impact of hereditary cancer gene panels on clinical care and lessons learned. 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