AnteMEL – Melanoma

Science behind AnteMEL

  • E-mail: info@antegenes.com
  • Phone number: +372 5377 8141

AnteMEL is a genetic test that assesses the personalized risk of developing melanoma using a polygenic risk score. AnteMEL is one of the tools for the prevention and early detection of melanoma. The purpose of the AnteMEL test is to reduce the risk of premature mortality due to melanoma by primary and secondary prevention.

AnteMEL has been developed by the healthcare and biotechnology company Antegenes (License number L04685) and is registered CE-marked medical device (IVD).

AnteMEL test uses data from single nucleotide polymorphisms (SNPs) in the genome to evaluate the personalized risk of developing melanoma. This approach is based on the methodology of polygenic risk scores. SNPs used in the risk score either increase or decrease the risk. AnteMEL combines the number of risk-increasing and lowering SNPs in the genome and their effects, which are summed up to form an overall estimate. Each SNP has little impact on the overall risk of melanoma, but combining the effects of individual SNPs contributes to a clinically significant assessment of the risk of developing melanoma.

The risk model is based on peer-reviewed international research and has been evaluated and validated using anonymous population data of the UK Biobank.

AnteMEL is used to determine the number of genetic variants that affect a patient’s individual risk and results in a combined genetic risk assessment. The patient’s personal risk is compared with the rest of the population, evaluating the 10-year probability of developing the disease and relative risk compared to the average genetic risk in the population, which is used to interpret the test results together with clinical recommendations.

Recommendations based on the relative risk calculated using the AnteMEL test consider only the polygenic risk component. In addition to test results, recommendations include clinical information about melanoma symptoms and indications for testing for the monogenic mutations.

Target Population

AnteMEL test is recommended for:

  • Men and women between the ages of 18 and 70 of European descent (Explanation: genetic risk studies used by AnteMEL have been conducted in populations of European descent).

The AnteMEL test is not recommended if:

  • The patient has a monogenic mutation, significantly increasing the risk of melanoma (BRCA2, CDKN2A, CDK4, TP53, PTEN).

Indications for testing for the monogenic mutations: 

  • The patient’s biological relative has a monogenic mutation of melanoma (BRCA2, CDKN2A, CDK4, TP53, PTEN);
  • Two or more biological relatives have been diagnosed with melanoma;
  • Biological relatives have had three or more tumors associated with hereditary cancer syndromes.

If these criteria are met, we recommend genetic counseling and, where appropriate, testing for hereditary forms of cancer.

Test Development

Population distribution of the polygenic risk score and risk differentiation were validated using anonymous data from the UK Biobank. Based on large-scale genetic data, various risk prediction models published in the international scientific literature were tested, and the prediction accuracy of the best performing model was evaluated on independent data. Based on the selected risk score, the population distribution on which the comparisons are based on was also created. The risk score underlying AnteMEL is derived from Fritsche et al. 2019 (1), which combines genetic variants known to be associated with melanoma in the NHGRI-EBI GWAS Catalog (2) with those found in the Michigan Genomics Initiative. The risk score underlying AnteMEL (1) is tailored for practical use and independently validated. After validation, AnteMEL uses 28 melanoma-related SNPs to calculate personalized risk scores.

Interpretations based on individual risk scores are dependent on population data. AnteMEL estimates the distribution of individual risk levels relative to the rest of the population, using the population distribution and the risk differentiation between patients estimated during validation on Estonian Biobank data. The patient’s 10-year population-based risk is calculated using Choudhury et al. absolute risk assessment model (2). The model uses the estimation of risk differentiation from validation on the UK Biobank data as input.

In addition, we use specific population-based overall mortality and melanoma morbidity and mortality data to assess risks.

Clinical recommendations in AnteMEL test are based on evidence-based data on melanoma risk factors, screening, and preventive measures, and the corresponding recommendations of international organizations, which are tailored to the individual risk level resulting from the test.

AnteMEL Test Methodology

AnteMEL test uses a non-invasive buccal swab method to collect and isolate patient’s DNA.

The genetic material is analyzed using second-generation genotyping and carried out in the Core Facility of the Institute of Genomics, University of Tartu, which is certified by Illumina CSPro (Certified Service Provider). The Illumina Global Screening Array-24 (GSA) v3.0 chip and Illumina iSCAN sequencer are used for genotyping. The GSA chip has ̴̴762,000 markers. The whole analysis is performed according to the Illumina Infinium HTS (high-throughput screening) protocol (Illumina Inc, http://www.illumina.com; Document # 15045738 v04).

Quality-controlled markers resulting from genotyping are imputed using a 1000G panel with reference to the human genome GRCh37. Based on imputed genotype data, an individual risk score is calculated in the Antegenesis Information System.

The test report is made available to the patient and their treating. Interpretation of the results and clinical recommendations are added to the report.

 AnteMEL Test Limitations 

  • AnteMEL test is not used to diagnose melanoma.
  • AnteMEL test is not validated for use by individuals of non-European descent.
  • An elevated risk estimated by the AnteMEL test does not mean that the patient will develop melanoma during their lifetime. Also, a moderate or lower risk does not mean that the patient will not develop the disease.
  • AnteMEL test is patient-specific and does not assess the risk of the patient’s family and relatives, i.e. polygenic risk score-based disease risks may not be transmitted directly from parents to children.
  • AnteMEL test does not analyze rare pathogenic mutations in genes that significantly increase the risk of melanoma, such as CDKN2A, MC1R, CDK4, TP53, PTEN, BAP1, POT1, ACD, PARK2, TERF2IP, TERT, BRCA1, BRCA2, RB1.
  • The AnteMEL test is based on the most up-to-date scientific data, which may, however, be supplemented and changed in the future as additional information becomes available. The field of genetics is constantly evolving, which may lead to changes in risk assessments over time, as well as changes in test selection recommendations and clinical recommendations based on test results.
  • Different polygenic risk scores predicting risks of the same trait may give different estimates of the individual’s risks due to differences in the genetic variants included in the models and their weights.
  • The results of this test should be applied in context with other relevant clinical data. In addition to the possible genetic predisposition, other risk factors also influence the risk of skin melanoma.

Cost of the test

Please see the “Customer Price List”.

References

  1. Fritsche LG, Beesley LJ, VandeHaar P, Peng RB, Salvatore M, Zawistowski M, et al. Exploring various polygenic risk scores for skin cancer in the phenomes of the Michigan genomics initiative and the UK Biobank with a visual catalog: PRSWeb. PLoS Genet. 2019;15(6):e1008202.
  2. MacArthur J, et al. . “The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog).” Nucleic acids research 45.D1 (2016): D896-D901.
  3. Choudhury PP, Maas P, Wilcox A, Wheeler W, Brook M, Check D, et al. iCARE: R package to build, validate and apply absolute risk models. bioRxiv. 2018:079954.