CM-Score: a validated scoring system to predict CDKN2A germline mutations in melanoma families from Northern Europe
| Autor: | Potjer, T.P., Helgadottir, H., Leenheer, M., Stoep, N. van der, Gruis, N.A., Hoiom, V., Olsson, H., Doorn, R. van, Vasen, H.F.A., Asperen, C.J. van, Dekkers, O.M., Hes, F.J., Dutch Working Grp Clinical Onc |
|---|---|
| Přispěvatelé: | Medical Genetics |
| Rok vydání: | 2018 |
| Předmět: |
cancer: head and neck
0301 basic medicine Oncology medicine.medical_specialty genetic epidemiology Logistic regression head and neck 03 medical and health sciences 0302 clinical medicine Germline mutation cancer: dermatological CDKN2A Internal medicine Genetics Medicine neoplasms Genetics (clinical) Cancer Medicine(all) business.industry Area under the curve genetic screening/counselling genetic screening medicine.disease counselling CM-Score 030104 developmental biology Genetic epidemiology 030220 oncology & carcinogenesis Cohort Medical genetics business clinical genetics Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] |
| Zdroj: | Journal of Medical Genetics, 55(10), 661-668 Journal of Medical Genetics, 55, 10, pp. 661-668 Journal of Medical Genetics, 55, 661-668 |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmedgenet-2017-105205 |
| Popis: | BackgroundSeveral factors have been reported that influence the probability of a germline CDKN2A mutation in a melanoma family. Our goal was to create a scoring system to estimate this probability, based on a set of clinical features present in the patient and his or her family.MethodsFive clinical features and their association with CDKN2A mutations were investigated in a training cohort of 1227 Dutch melanoma families (13.7% with CDKN2A mutation) using multivariate logistic regression. Predefined features included number of family members with melanoma and with multiple primary melanomas, median age at diagnosis and presence of pancreatic cancer or upper airway cancer in a family member. Based on these five features, a scoring system (CDKN2A Mutation(CM)-Score) was developed and subsequently validated in a combined Swedish and Dutch familial melanoma cohort (n=421 families; 9.0% with CDKN2A mutation).ResultsAll five features were significantly associated (pCDKN2A mutation. At a CM-Score of 16 out of 49 possible points, the threshold of 10% mutation probability is approximated (9.9%; 95% CI 9.8 to 10.1). This probability further increased to >90% for families with ≥36 points. A CM-Score under 16 points was associated with a low mutation probability (≤4%). CM-Score performed well in both the training cohort (area under the curve (AUC) 0.89; 95% CI 0.86 to 0.92) and the external validation cohort (AUC 0.94; 95% CI 0.90 to 0.98).ConclusionWe developed a practical scoring system to predict CDKN2A mutation status among melanoma-prone families. We suggest that CDKN2A analysis should be recommended to families with a CM-Score of ≥16 points. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|