Blair VR, McLeod M, Carneiro F et al (2020) Hereditary diffuse gastric cancer: updated clinical practice guidelines. Lancet Oncol 21:e386–e397. https://doi.org/10.1016/S1470-2045(20)30219-9

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hansford S, Kaurah P, Li-Chang H et al (2015) Hereditary diffuse gastric Cancer syndrome: CDH1 mutations and Beyond. JAMA Oncol 1:23–32. https://doi.org/10.1001/jamaoncol.2014.168

Article  PubMed  Google Scholar 

Lobo S, Benusiglio PR, Coulet F et al (2021) Cancer predisposition and germline CTNNA1 variants. Eur J Med Genet 64:104316. https://doi.org/10.1016/j.ejmg.2021.104316

Article  CAS  PubMed  Google Scholar 

Clark DF, Michalski ST, Tondon R et al (2020) Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer. Genet Med 22:840–846. https://doi.org/10.1038/s41436-020-0753-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pharoah PD, Guilford P, Caldas C, International Gastric Cancer Linkage Consortium (2001) Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 121:1348–1353. https://doi.org/10.1053/gast.2001.29611

Article  CAS  PubMed  Google Scholar 

Xicola RM, Li S, Rodriguez N et al (2019) Clinical features and cancer risk in families with pathogenic CDH1 variants irrespective of clinical criteria. J Med Genet 56:838–843. https://doi.org/10.1136/jmedgenet-2019-105991

Article  CAS  PubMed  Google Scholar 

Roberts ME, Ranola JMO, Marshall ML et al (2019) Comparison of CDH1 Penetrance estimates in clinically ascertained families vs families ascertained for multiple gastric cancers. JAMA Oncol 5:1325–1331. https://doi.org/10.1001/jamaoncol.2019.1208

Article  PubMed  PubMed Central  Google Scholar 

Lowstuter K, Espenschied CR, Sturgeon D et al (2017) Unexpected CDH1 mutations identified on Multigene Panels Pose Clinical Management Challenges. JCO Precis Oncol 1:1–12. https://doi.org/10.1200/PO.16.00021

Article  PubMed  Google Scholar 

Katona BW, Clark DF, Domchek SM (2020) CDH1 on Multigene Panel Testing: look before you Leap. J Natl Cancer Inst 112:330–334. https://doi.org/10.1093/jnci/djz229

Article  PubMed  Google Scholar 

Daly MB et al (2023) PTAZ. National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.

Manahan ER, Kuerer HM, Sebastian M, Hughes KS, Boughey JC, Euhus DM, Boolbol SK, Taylor WA (2019) Consensus Guidelines on Genetic` testing for Hereditary breast Cancer from the american society of breast surgeons. Ann Surg Oncol 26:3025–3031. https://doi.org/10.1245/s10434-019-07549-8

Article  PubMed  PubMed Central  Google Scholar 

Federici G, Soddu S (2020) Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers. J Experimental Clin Cancer Res 39:46. https://doi.org/10.1186/s13046-020-01554-6

Idos GE, Kurian AW, Ricker C et al (2019) Multicenter prospective cohort study of the Diagnostic yield and patient experience of Multiplex Gene Panel Testing for Hereditary Cancer Risk. https://doi.org/10.1200/po.18.00217. JCO Precis Oncol

Mighton C, Shickh S, Uleryk E et al (2021) Clinical and psychological outcomes of receiving a variant of uncertain significance from multigene panel testing or genomic sequencing: a systematic review and meta-analysis. Genet Sci 23:22–33. https://doi.org/10.1038/s41436-020-00957-2

Article  Google Scholar 

Lerner BA, Xicola RM, Rodriguez NJ, Karam R, Llor X (2023) Simplified and more sensitive criteria for identifying individuals with pathogenic CDH1 variants. J Med Genet 60:36–40. https://doi.org/10.1136/jmedgenet-2021-108169

Article  PubMed  Google Scholar 

Rofes P, Menéndez M, González S et al (2020) Improving genetic testing in Hereditary Cancer by RNA analysis: tools to prioritize Splicing Studies and Challenges in applying American College of Medical Genetics and Genomics Guidelines. J Mol Diagn 22:1453–1468. https://doi.org/10.1016/j.jmoldx.2020.09.007

Article  CAS  PubMed  Google Scholar 

Karam R, Conner B, LaDuca H et al (2019) Assessment of Diagnostic Outcomes of RNA genetic testing for Hereditary Cancer. JAMA Netw Open 2:e1913900. https://doi.org/10.1001/jamanetworkopen.2019.13900

Article  PubMed  PubMed Central  Google Scholar 

Scotti MM, Swanson MS (2016) RNA mis-splicing in disease. Nat Rev Genet 17:19–32. https://doi.org/10.1038/nrg.2015.3

Article  CAS  PubMed  Google Scholar 

Rhine CL, Cygan KJ, Soemedi R et al (2018) Hereditary cancer genes are highly susceptible to splicing mutations. PLoS Genet 14:e1007231. https://doi.org/10.1371/journal.pgen.1007231

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barbosa-Matos R, Silva L, Garrido R, L. et al (2021) The CDH1 c.1901 C > T variant: a founder variant in the Portuguese Population with severe impact in mRNA splicing. Cancers 13:4464. https://doi.org/10.3390/cancers13174464

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaurah P, MacMillan A, Boyd N et al (2007) Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA 297(21):2360–2372. https://doi.org/10.1001/jama.297.21.2360

Article  CAS  PubMed  Google Scholar 

Gamble LA, Rossi A, Fasaye GA et al (2022) Association between Hereditary lobular breast Cancer due to CDH1 variants and gastric Cancer risk. JAMA Surg 157:18–22. https://doi.org/10.1001/jamasurg.2021.5118

Article  PubMed  Google Scholar 

Garcia-Pelaez J, Barbosa-Matos R, Lobo S et al (2023) Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the european Reference Network on genetic Tumour Risk Syndromes. Lancet Oncol 1:91–106. https://doi.org/10.1016/S1470-2045(22)00643-X

Article  Google Scholar 

Lecuit T, Yap AS (2015) E-cadherin junctions as active mechanical integrators in tissue dynamics. Nat Cell Biol 17:533–539. https://doi.org/10.1038/ncb3136

Article  CAS  PubMed  Google Scholar 

Oliveira C, Senz J, Kaurah P et al (2009) Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet 18:1545–1555. https://doi.org/10.1093/hmg/ddp046

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee K, Krempely K, Roberts ME, Anderson MJ et al (2018) Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants. Hum Mutat 39:1553–1568. https://doi.org/10.1002/humu.23650

Article  PubMed  PubMed Central  Google Scholar 

Luo X, Maciaszek JL, Thompson BA et al (2023) ClinGen CDH1 variant Curation Expert Panel. Optimising clinical care through CDH1-specific germline variant curation: improvement of clinical assertions and updated curation guidelines. J Med Genet 60:568–575. https://doi.org/10.1136/jmg-2022-108807

Article  PubMed  Google Scholar 

Horton C, Cass A, Conner BR et al (2022) Mutational and splicing landscape in a cohort of 43,000 patients tested for hereditary cancer. NPJ Genom Med 7:49. https://doi.org/10.1038/s41525-022-00323-y

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jaganathan K, Kyriazopoulou Panagiotopoulou S, McRae JF et al (2019) Predicting Splicing from primary sequence with deep learning. Cell 176:535–548e24. https://doi.org/10.1016/j.cell.2018.12.015

Article  CAS  PubMed  Google Scholar 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet medicine: official J Am Coll Med Genet 17:405–424. https://doi.org/10.1038/gim.2015.30

Article  Google Scholar 

Karczewski KJ, Francioli LC, Tiao G et al (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:434–443. https://doi.org/10.1038/s41586-020-2308-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

Asif B, Sarvestani AL, Gamble LA, Samaranayake SG, Famiglietti AL, Fasaye GA, Quezado M, Miettinen M, Korman L, Koh C, Heller T, Davis JL (2023) Cancer surveillance as an alternative to prophylactic total gastrectomy in hereditary diffuse gastric cancer: a prospective cohort study. Lancet Oncol 24:383–391. https://doi.org/10.1016/S1470-2045(23)00057-8

Article  PubMed  Google Scholar 

Lee CYC, Olivier A, Honing J, Lydon AM, Richardson S, O’Donovan M, Tischkowitz M, Fitzgerald RC, di Pietro M (2023) Endoscopic surveillance with systematic random biopsy for the early diagnosis of hereditary diffuse gastric cancer: a prospective 16-year longitudinal cohort study. Lancet Oncol 24:107–116. https://doi.org/10.1016/S1470-2045(22)00700-8

Article  CAS  PubMed  Google Scholar 

Henrie A, Hemphill SE, Ruiz-Schultz N et al (2018) ClinVar Miner: demonstrating utility of a web-based tool for viewing and filtering ClinVar data. Hum Mutat 39:1051–1060. https://doi.org/10.1002/humu.23555

Article  PubMed  PubMed Central  Google Scholar 

Mersch J, Brown N, Pirzadeh-Miller S et al (2018) Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA - Journal of the American Medical Association 320:1266–1274. https://doi.org/10.1001/jama.2018.13152

Article  PubMed  Google Scholar 

Slavin TP, Manjarrez S, Pritchard CC et al (2019) The effects of genomic germline variant reclassification on clinical cancer care. Oncotarget 10:417–423. https://doi.org/10.18632/oncotarget.26501

Article  PubMed  PubMed Central  Google Scholar 

Casaletto J, Cline M, Shirts B (2023) Modeling the impact of data sharing on variant classification. J Am Med Inform Assoc 30:466–474. https://doi.org/10.1093/jamia/ocac232

Article  PubMed  Google Scholar 

Vadaparampil ST, Scherr CL, Cragun D et al (2015) Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by non-genetics professionals in the state of Florida. Clin Genet 87:473–477. https://doi.org/10.1111/cge.12405