Retinoblastoma — the most common intraocular cancer of childhood, where germline RB1 status determines second cancer surveillance for the rest of a survivor's life.
Whole genome sequencing identifies all RB1 variant types — including mosaic mutations that standard blood-based testing may miss — and resolves the germline vs. somatic question that determines lifetime cancer surveillance needs.
Retinoblastoma
Retinoblastoma (Rb) is the most common intraocular malignancy of childhood, affecting approximately 1 in 15,000-20,000 live births, with approximately 8,000 new cases diagnosed annually worldwide. It arises from the retinoblasts, immature precursor cells of the retina, due to biallelic inactivation of the RB1 tumor suppressor gene on chromosome 13q14.2 — the first tumor suppressor gene characterized at the molecular level. Retinoblastoma presents with leukocoria (white pupillary reflex), strabismus, and vision loss, usually in children under 5 years. With current treatment, overall survival exceeds 95% in high-income countries, though outcomes vary substantially by disease stage and resource availability.
Approximately 40% of retinoblastoma cases are hereditary — caused by a germline (constitutional) pathogenic variant in RB1. Hereditary retinoblastoma is typically bilateral (75-80%) or multifocal, with median age of diagnosis younger than sporadic cases. The remaining ~60% of cases are sporadic (non-hereditary), caused by two somatic RB1 hits in a single retinal cell. Unilateral retinoblastoma may be hereditary or sporadic — approximately 15% of unilateral cases have germline RB1 variants, a proportion that rises to nearly 100% in bilateral cases. Approximately 10-15% of unilateral retinoblastoma without a detectable germline variant carry somatic mosaic RB1 mutations detectable only in tumor or in deep blood sequencing.
The critical distinction between hereditary and non-hereditary retinoblastoma lies not in the eye tumor prognosis, but in lifetime second cancer risk. Hereditary RB1 carriers have an estimated 50% cumulative risk of a second primary cancer by age 50, predominantly radiation-field related osteosarcomas, soft tissue sarcomas, and melanoma. This risk is substantially elevated by radiation therapy, which is avoided where possible in germline RB1 carriers. Surviving hereditary retinoblastoma triggers a lifetime surveillance protocol: regular imaging for soft tissue and bone tumors, avoidance of UV radiation, and cascade genetic testing of offspring with ophthalmic examination in infancy. Gene therapy and targeted RB1 pathway approaches are under investigation.
Mosaic RB1 mutations — where the germline variant is present in only a fraction of cells — occur in approximately 10-12% of hereditary retinoblastoma and may be missed by standard blood-based sequencing. Deep sequencing and tumor tissue analysis improve detection.
Determining germline vs. somatic mosaic RB1 status requires both blood and tumor tissue analysis at sequencing depths standard panels may not achieve. Mosaic variants in blood at 5-20% allele fraction are missed by conventional testing.
Mosaic RB1 variants are missed by standard germline testing — and have clinical consequences for the entire family
Somatic mosaicism in retinoblastoma — where the RB1 pathogenic variant arose post-zygotically and is present in only a subset of cells — affects approximately 10-12% of hereditary cases. Parents of an index patient with mosaic RB1 may themselves have mosaic mosaicism at very low variant allele fractions. Standard exome and panel sequencing is calibrated for germline heterozygous variants at ~50% allele fraction; mosaic variants present at 10-20% may fall below the variant calling threshold. Deep whole genome sequencing with enhanced sensitivity for low-allele-fraction variants improves mosaic detection. Missing a mosaic germline RB1 variant in a parent would lead to incorrect recurrence risk counseling — presenting the next pregnancy as no-risk when in fact the parent can transmit the variant.
Germline RB1 status determines radiation therapy decisions during tumor treatment
External beam radiation therapy for retinoblastoma substantially increases second primary cancer risk in germline RB1 carriers in the radiation field — particularly osteosarcoma of the orbital region. For this reason, current management of hereditary retinoblastoma strongly favors non-radiation-based approaches (intra-arterial chemotherapy, intravitreous melphalan, focal treatments) when feasible, specifically to avoid the radiation-associated second cancer risk. Making this treatment decision requires knowing germline RB1 status at the time of initial treatment — not years later when a second cancer develops. Whole genome sequencing provides the complete RB1 genotype, including mosaic detection, to inform treatment planning from day one.
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.
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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.
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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.
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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
