ArticleHuman molecular genetics2009
Germline CDH1 deletions in hereditary diffuse gastric cancer families.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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Who cites it
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Hereditary diffuse gastric cancer: updated clinical practice guidelines.The Lancet. Oncology · 2020Guideline
- Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature.BMC cancer · 2012Pooled it
- Immune, molecular and genetic profiles of gastric signet ring cell carcinoma: Recent progress and future challenges.International journal of cancer · 2026Review
- Article
- Hereditary diffuse gastric cancer: the evolution of a cancer syndrome.Journal of the Royal Society of New Zealand · 2025Review
- Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses.NPJ genomic medicine · 2024Article
- Developing AAV-delivered nonsense suppressor tRNAs for neurological disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- System-wide identification of novel de-ubiquitination targets for USP10 in gastric cancer metastasis through multi-omics screening.BMC cancer · 2024Article
- Combining clinical and molecular characterization of CDH1: a multidisciplinary approach to reclassification of a splicing variant.Familial cancer · 2023Article
- Combined loss of CDH1 and downstream regulatory sequences drive early-onset diffuse gastric cancer and increase penetrance of hereditary diffuse gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Prenatal diagnosis of hereditary diffuse gastric cancer: a case report.BMC pregnancy and childbirth · 2023Article
- Current advances in understanding the molecular profile of hereditary diffuse gastric cancer and its clinical implications.Journal of experimental & clinical cancer research : CR · 2023Review
- 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.The Lancet. Oncology · 2023Article
- Hereditary Diffuse Gastric Cancer: A 2022 Update.Journal of personalized medicine · 2022Review
- Article
- Article
- Hereditary Diffuse Gastric Cancer: Molecular Genetics, Biological Mechanisms and Current Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Patient with prostatic adenocarcinoma with plasmacytoid features and an aberrant immunohistochemical phenotype diagnosed by biopsy and a mini-review of plasmacytoid features in the genitourinary system: A case report.Molecular and clinical oncology · 2022Article
- Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants.International journal of molecular sciences · 2022Review
- Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 12 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Germline CDH1 point or small frameshift mutations can be identified in 30-50% of hereditary diffuse gastric cancer (HDGC) families. We hypothesized that CDH1 genomic rearrangements would be found in HDGC and identified 160 families with either two gastric cancers in first-degree relatives and with at least one diffuse gastric cancer (DGC) diagnosed before age 50, or three or more DGC in close relatives diagnosed at any age. Sixty-seven carried germline CDH1 point or small frameshift mutations. We screened germline DNA from the 93 mutation negative probands for large genomic rearrangements by Multiplex Ligation-Dependent Probe Amplification. Potential deletions were validated by RT-PCR and breakpoints cloned using a combination of oligo-CGH-arrays and long-range-PCR. In-silico analysis of the CDH1 locus was used to determine a potential mechanism for these rearrangements. Six of 93 (6.5%) previously described mutation negative HDGC probands, from low GC incidence populations (UK and North America), carried genomic deletions (UK and North America). Two families carried an identical deletion spanning 193 593 bp, encompassing the full CDH3 sequence and CDH1 exons 1 and 2. Other deletions affecting exons 1, 2, 15 and/or 16 were identified. The statistically significant over-representation of Alus around breakpoints indicates it as a likely mechanism for these deletions. When all mutations and deletions are considered, the overall frequency of CDH1 alterations in HDGC is approximately 46% (73/160). CDH1 large deletions occur in 4% of HDGC families by mechanisms involving mainly non-allelic homologous recombination in Alu repeat sequences. As the finding of pathogenic CDH1 mutations is useful for management of HDGC families, screening for deletions should be offered to at-risk families.
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Registered trials
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