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Efficiency of BRCAPRO and Myriad II mutation probability thresholds versus cancer history criteria alone for BRCA1/2 mutation detection

By J. J. T. van Harssel, C. E. P. van Roozendaal, Y. Detisch, R. D. Brandão, A. D. C. Paulussen, M. Zeegers, M. J. Blok and E. B. Gómez García

Abstract

Considerable differences exist amongst countries in the mutation probability methods and thresholds used to select patients for BRCA1/2 genetic screening. In order to assess the added value of mutation probability methods, we have retrospectively calculated the BRCAPRO and Myriad II probabilities in 306 probands who had previously been selected for DNA-analysis according to criteria based on familial history of cancer. DNA-analysis identified 52 mutations (16.9%) and 11 unclassified variants (UVs, 3.6%). Compared to cancer history, a threshold ≥10% with BRCAPRO or with Myriad II excluded about 40% of the patients from analysis, including four with a mutation and probabilities <10% with both programs. All four probands had a BRCA2 mutation. BRCAPRO and Myriad II showed similar specificity at 10% threshold, overall BRCAPRO was more sensitive than Myriad II for the detection of mutations. Only two of the probands with an UV had probabilities >20% with BRCAPRO and Myriad II. In summary, BRCAPRO and Myriad II are more efficient than cancer history alone to exclude patients without a mutation. BRCAPRO performs better for the detection of BRCA1 mutations than of BRCA2 mutations. The Myriad II scores provided no additional information than the BRCAPRO scores alone for the detection of patients with a mutation. The use of thresholds excluded from analysis the majority of patients carrying an UV

Topics: Article
Publisher: Springer Netherlands
OAI identifier: oai:pubmedcentral.nih.gov:2871096
Provided by: PubMed Central

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Citations

  1. (2009). A method to assess the clinical significance of unclassified variants (UVs) in the BRCA1 and BRCA2 genes based on cancer family history.
  2. (2004). A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO.
  3. (1994). A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
  4. (2005). Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations.
  5. (2003). Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies.
  6. (1997). BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer.
  7. (1997). BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing.
  8. (1995). Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast cancer linkage consortium.
  9. (2003). Breast and ovarian cancer risks due to inherited mutations
  10. (2002). Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10, 000 individuals.
  11. (2005). den Wijngaard A
  12. (1999). Denaturing high-performance liquid chromatography detects reliably BRCA1 and BRCA2 mutations.
  13. (1998). Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2.
  14. (2006). for health and clinical Excellence
  15. (2008). Functional assays for classification of BRCA2 variants of uncertain signifi-cance.
  16. (2006). Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance.
  17. (1998). Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium.
  18. Gudbjartsson DF et al (2002) BRCAPRO validation, sensitivity of genetic testing of BRCA1/ BRCA2, and prevalence of other breast cancer susceptibility genes.
  19. (1995). Identification of the breast cancer susceptibility gene BRCA2.
  20. (2004). Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2.
  21. Kwaliteitsinstituut voor de Gezondheidszorg CBO, Vereniging van Integrale Kankercentra. Richtlijn mammacarcinoom.
  22. (2003). Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method.
  23. of Clinical Oncology policy statement update (2003) Genetic testing for cancer susceptibility.
  24. Ohashi A et al (2005) Functional evaluation and cancer risk assessment of BRCA2 unclassified variants.
  25. (1998). Olopade OI et al
  26. (2006). Optimal selection for BRCA1 and BRCA2 mutation testing using a combination of ‘easy to apply’ probability models.
  27. (2006). Optimal selection of individuals for BRCA mutation testing: a comparison of available methods.
  28. (2007). Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of LAMBDA, BRCAPRO, Myriad II, and modified Couch models.
  29. (2008). Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad II and the Manchester scoring system using data from UK genetics clinics.
  30. (2004). Structurebased assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition.
  31. (1996). the American Society of Clinical Oncology
  32. (2004). The BOADICEA model of genetic susceptibility to breast and ovarian cancer.
  33. (2001). Variation in cancer risks, by mutation position, in BRCA2 mutation carriers.