Hereditary Diffuse Gastric Cancer — CDH1 loss-of-function carrying up to 70% lifetime gastric cancer risk, where the cancer develops beneath the gastric mucosa and is invisible to endoscopy until it is surgically unresectable.
Whole genome sequencing identifies all CDH1 variants — including large deletions and mosaic mutations — to establish the diagnosis that triggers the prophylactic total gastrectomy recommendation before an endoscopically invisible cancer advances.
Hereditary Diffuse Gastric Cancer
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer predisposition syndrome caused by pathogenic variants in CDH1 (E-cadherin) on chromosome 16q22.1. CDH1 encodes a cell-cell adhesion protein critical for epithelial integrity; its loss-of-function leads to the poorly cohesive, infiltrating growth pattern characteristic of diffuse gastric cancer (signet ring cell carcinoma). HDGC was first defined in 1998 in a large Maori kindred from New Zealand, and remains one of the most lethal hereditary cancer syndromes — lifetime gastric cancer risk in CDH1 pathogenic variant carriers is estimated at 40-70% in males and 45-70% in females. The median age of onset in familial cases is 38 years, but cases have been documented in patients in their 20s.
The clinical challenge of HDGC is that diffuse gastric cancer grows as individual signet ring cells infiltrating the submucosa — a growth pattern that does not form a visible mass and cannot be reliably detected by standard endoscopy. Endoscopic surveillance, even with systematic biopsy protocols, misses the majority of early HDGC lesions. Every total gastrectomy performed prophylactically in CDH1 pathogenic variant carriers reveals occult signet ring cell foci on pathology — meaning that even 'normal' appearing stomachs harbor microscopic cancer in virtually all carriers. This single biological fact drives the recommendation for prophylactic total gastrectomy for CDH1 carriers between ages 18-40, rather than surveillance.
Female CDH1 carriers also face substantially elevated lobular breast cancer risk — estimated at 42-56% lifetime. Lobular breast cancer, like diffuse gastric cancer, grows in an infiltrating single-file pattern that standard mammography may not detect, making breast MRI an essential component of surveillance. CDH1 is included in the ACMG SF v3.2 secondary findings list, reflecting consensus that identifying CDH1 carriers before cancer develops is both clinically actionable and life-saving. Approximately 40% of families meeting clinical HDGC criteria are CDH1-negative; some of these families have variants in CTNNA1 (alpha-E-catenin) or other genes, and a comprehensive genomic approach is indicated.
Standard hereditary cancer panels miss large CDH1 deletions and mosaic variants. In a syndrome where prophylactic surgery depends on molecular confirmation, an incomplete genetic result has direct surgical consequences.
Large CDH1 deletions account for 10-15% of HDGC and are missed by exon-sequencing panels
Approximately 10-15% of CDH1 pathogenic variants in HDGC families are large genomic deletions spanning one or more exons. Exon-sequencing panels that do not include deletion/duplication analysis by MLPA or copy number variant calling will miss these variants. Additionally, somatic mosaicism — where the CDH1 variant is present in only a fraction of the patient's cells — has been documented in some families and may be missed by standard sequencing depths. Whole genome sequencing provides simultaneous point mutation detection and copy number variant analysis across the entire CDH1 gene, resolving both common intragenic variants and structural rearrangements in a single test.
Prophylactic gastrectomy requires molecular confirmation — a negative panel result is not the same as a true negative
Total gastrectomy is a major surgical procedure with significant long-term quality of life implications. It is recommended in CDH1 carriers because early-stage diffuse gastric cancer is endoscopically invisible and surveillance has failed to prevent deaths in known carrier families. This recommendation is only appropriate when molecular confirmation of a CDH1 pathogenic variant is established. An incomplete panel that did not evaluate large deletions or perform comprehensive CDH1 analysis provides false reassurance to a family where the pathogenic variant may still exist but was simply not detectable by limited testing. Whole genome sequencing removes this ambiguity.
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
Comprehensive insights and specialized reports
Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
Your test becomes more valuable every year
Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
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Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Hereditary Diffuse Gastric Cancer and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
- Custom genomic reports for your members
- Group discounts and tailored packages
- Any country — including virtual groups
- Rare and common conditions covered
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One test.
A lifetime of answers.
One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
