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Journal of Genetic Counseling

, Volume 23, Issue 4, pp 633–639 | Cite as

The Evolution of Cancer Risk Assessment in the Era of Next Generation Sequencing

  • Heather FecteauEmail author
  • Kristen J. Vogel
  • Kristen Hanson
  • Shannon Morrill-Cornelius
NEXT GENERATION GENETIC COUNSELING

Abstract

Cancer genetics professionals face a new opportunity and challenge in adapting to the availability of cancer genetic testing panels, now available as a result of Next Generation Sequencing (NGS) technology. While cancer panels have been available for over a year, we believe that there is not yet enough data to create practice guidelines. Despite this, a year of experience allows us to provide our opinion on points to consider as cancer genetic counselors incorporate this testing technology into genetic counseling practice models. NGS technology offers the ability to potentially diagnose hereditary cancer syndromes more efficiently by testing many genes at once for a fraction of what it would cost to test each gene individually. However, there are limitations and additional risks to consider with these tests. Obtaining informed consent for concurrent testing of multiple genes requires that genetics professionals modify their discussions with patients regarding the potential cancer risks and the associated implications to medical management. We propose dividing the genes on each panel into categories that vary by degree of cancer risk (e.g. penetrance of the syndrome) and availability of management guidelines, with the aim to improve patient understanding of the range of information that can come from this testing. The increased risk for identifying variants of uncertain significance (VUS) when testing many genes at once must be discussed with patients. Pretest genetic counseling must also include the possibility to receive unexpected results as well as the potential to receive a result in the absence of related medical management guidelines. It is also important to consider whether a single gene test remains the best testing option for some patients. As panels expand, it is important that documentation reflects exactly which genes have been analyzed for each patient. While this technology holds the promise of more efficient diagnosis for many of our patients, it also comes with new challenges that we must recognize and address.

Keywords

Genetic counseling Neoplastic syndromes Hereditary Genetics Medical Next generation sequencing Genetic testing panels 

Notes

Conflict of Interest

Heather Fecteau MS, CGC, Kristen Vogel MS, CGC, Kristen Hanson MS, CGC, and Shannon Morrill-Cornelius MS, CGC declare that they have no conflict of interest.

Human and Animal Rights

No animal or human studies were carried out by the authors for this article.

References

  1. Ackerman, M. J., Priori, S. G., Willems, S., Berul, C., Brugada, R., Calkins, H., et al. (2011). HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm, 8(8), 1308–1339. doi: https://doi.org/10.1016/j.hrthm.2011.05.020.Google Scholar
  2. ACMG Board of Directors. (2012). Points to consider in the clinical application of genomic sequencing. Genetics in Medicine, 14(8), 759–761. doi: https://doi.org/10.1038/gim.2012.74.Google Scholar
  3. Birch, J. M., Alston, R. D., McNally, R. J., Evans, D. G., Kelsey, A. M., Harris, M., et al. (2001). Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene, 20(34), 4621–4628. doi: https://doi.org/10.1038/sj.onc.1204621.PubMedPubMedCentralGoogle Scholar
  4. Casadei, S., Norquist, B. M., Walsh, T., Stray, S., Mandell, J. B., Lee, M. K., et al. (2011). Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Research, 71(6), 2222–2229. doi: https://doi.org/10.1158/0008-5472.can-10-3958.PubMedPubMedCentralGoogle Scholar
  5. Chompret, A., Brugieres, L., Ronsin, M., Gardes, M., Dessarps-Freichey, F., Abel, A., et al. (2000). P53 germline mutations in childhood cancers and cancer risk for carrier individuals. British Journal of Cancer, 82(12), 1932–1937. doi: https://doi.org/10.1054/bjoc.2000.1167.PubMedPubMedCentralGoogle Scholar
  6. Domchek, S., & Weber, B. L. (2008). Genetic Variants of uncertain significance: flies in the ointment. Journal of Clinical Oncology, 26(1), 16–17. doi: https://doi.org/10.1200/JCO.2007.14.4154.PubMedPubMedCentralGoogle Scholar
  7. Domchek, S. M., Bradbury, A., Garber, J. E., Offit, K., & Robson, M. E. (2013). Multiplex genetic testing for cancer susceptibility: out on the high wire without a net? Journal of Clinical Oncology, 31(10), 1267–1270. doi: https://doi.org/10.1200/jco.2012.46.9403.PubMedPubMedCentralGoogle Scholar
  8. Erkko, H., Xia, B., Nikkila, J., Schleutker, J., Syrjakoski, K., Mannermaa, A., et al. (2007). A recurrent mutation in PALB2 in Finnish cancer families. Nature, 446(7133), 316–319. doi: https://doi.org/10.1038/nature05609.PubMedPubMedCentralGoogle Scholar
  9. Frank, B., Hemminki, K., Meindl, A., Wappenschmidt, B., Sutter, C., Kiechle, M., et al. (2007). BRIP1 (BACH1) variants and familial breast cancer risk: a case–control study. BMC Cancer, 7, 83. doi: https://doi.org/10.1186/1471-2407-7-83.PubMedPubMedCentralGoogle Scholar
  10. Gonzalez, K. D., Noltner, K. A., Buzin, C. H., Gu, D., Wen-Fong, C. Y., Nguyen, V. Q., et al. (2009). Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. Journal of Clinical Oncology, 27(8), 1250–1256. doi: https://doi.org/10.1200/jco.2008.16.6959.PubMedPubMedCentralGoogle Scholar
  11. Halbert, C. H., Stopfer, J. E., McDonald, J., Weathers, B., Collier, A., Troxel, A. B., et al. (2011). Long-term reactions to genetic testing for BRCA1 and BRCA2 mutations: does time heal women’s concerns? Journal of Clinical Oncology, 29(32), 4302–4306. doi: https://doi.org/10.1200/jco.2010.33.1561.PubMedPubMedCentralGoogle Scholar
  12. Hamilton, J. G., Lobel, M., & Moyer, A. (2009). Emotional distress following genetic testing for hereditary breast and ovarian cancer: a meta-analytic review. Health Psychology, 28(4), 510–518. doi: https://doi.org/10.1037/a0014778.PubMedPubMedCentralGoogle Scholar
  13. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, “Genetic/Familial High-Risk Assessment: Breast and Ovarian,” 2013, https://doi.org/www.nccn.org/index.asp.
  14. Jones, S., Hruban, R. H., Kamiyama, M., Borges, M., Zhang, X., Parsons, D. W., et al. (2009). Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science, 324(5924), 217. doi: https://doi.org/10.1126/science.1171202.PubMedPubMedCentralGoogle Scholar
  15. Kleihues, P., Schauble, B., Zur Hausen, A., Esteve, J., & Ohgaki, H. (1997). Tumors associated with p53 germline mutations: a synopsis of 91 families. The American Journal of Pathology, 150(1), 1–13.PubMedPubMedCentralGoogle Scholar
  16. Lewis, A. G., Flanagan, J., Marsh, A., Pupo, G. M., Mann, G., Spurdle, A. B., et al. (2005). Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer. Breast Cancer Research, 7(6), R1005–R1016. doi: https://doi.org/10.1186/bcr1336.PubMedPubMedCentralGoogle Scholar
  17. Li, F. P., Fraumeni, J. F., Jr., Mulvihill, J. J., Blattner, W. A., Dreyfus, M. G., Tucker, M. A., et al. (1988). A cancer family syndrome in twenty-four kindreds. Cancer Research, 48(18), 5358–5362.PubMedPubMedCentralGoogle Scholar
  18. Meldrum, C., Doyle, M. A., & Tothill, R. W. (2011). Next-generation sequencing for cancer diagnostics: a practical perspective. Clinical Biochemistry Reviews, 32(4), 177–195.Google Scholar
  19. Nichols, K. E., Malkin, D., Garber, J. E., Fraumeni, J. F., Jr., & Li, F. P. (2001). Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiology, Biomarkers and Prevention, 10(2), 83–87.PubMedPubMedCentralGoogle Scholar
  20. Offit, K. (2011). Personalized medicine: new genomics, old lessons. Human Genetics, 130(1), 3–14. doi: https://doi.org/10.1007/s00439-011-1028-3.PubMedPubMedCentralGoogle Scholar
  21. Pletcher, B. A., Toriello, H. V., Noblin, S. J., Seaver, L. H., Driscool, D. A., Bennett, R. L., et al. (2007). Indications for genetic referral: a guide for health care professionals. Genetics in Medicine, 9(6), 385–389.PubMedPubMedCentralGoogle Scholar
  22. U.S. Preventive Services Task Force (2014). Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: Recommendations From the U.S. Preventive Services Task Force. Annals of Internal Medicine 160 (4), I-16-16.Google Scholar
  23. Rafnar, T., Gudbjartsson, D. F., Sulem, P., Jonasdottir, A., Sigurdsson, A., Jonasdottir, A., et al. (2011). Mutations in BRIP1 confer high risk of ovarian cancer. Nature Genetics, 43(11), 1104–1107. doi: https://doi.org/10.1038/ng.955.PubMedPubMedCentralGoogle Scholar
  24. Rahman, N., Seal, S., Thompson, D., Kelly, P., Renwick, A., Elliott, A., et al. (2007). PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nature Genetics, 39(2), 165–167. doi: https://doi.org/10.1038/ng1959.PubMedPubMedCentralGoogle Scholar
  25. Rehm, H. L., Bale, S. J., Bayrak-Toydemir, P., Berg, J. S., Brown, K. K., Deignan, J. L., et al. (2013). ACMG clinical laboratory standards for next-generation sequencing. Genetics in Medicine, 15(9), 733–747. doi: https://doi.org/10.1038/gim.2013.92.PubMedPubMedCentralGoogle Scholar
  26. Robson, M. E., Storm, C. D., Weitzel, J., Wollins, D. S., & Offit, K. (2010). American society of clinical oncology policy statement update: Genetic and genomic testing for cancer susceptibility. Journal of Clinical Oncology, 28(5), 893–901.PubMedPubMedCentralGoogle Scholar
  27. Seal, S., Thompson, D., Renwick, A., Elliott, A., Kelly, P., Barfoot, R., et al. (2006). Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nature Genetics, 38(11), 1239–1241. doi: https://doi.org/10.1038/ng1902.PubMedPubMedCentralGoogle Scholar
  28. Villani, A., Tabori, U., Schiffman, J., Shlien, A., Beyene, J., Druker, H., et al. (2011). Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. The Lancet Oncology, 12(6), 559–567. doi: https://doi.org/10.1016/s1470-2045(11)70119-x.PubMedPubMedCentralGoogle Scholar
  29. Walsh, T., Casadei, S., Lee, M. K., Pennil, C. C., Nord, A. S., Thornton, A. M., et al. (2011). Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proceedings of the National Academy of Sciences of the United States of America, 108(44), 18032–18037. doi: https://doi.org/10.1073/pnas.1115052108.PubMedPubMedCentralGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2014

Authors and Affiliations

  • Heather Fecteau
    • 1
    Email author
  • Kristen J. Vogel
    • 2
  • Kristen Hanson
    • 3
  • Shannon Morrill-Cornelius
    • 4
  1. 1.The Medical Center of PlanoDallasUSA
  2. 2.North Shore University Health SystemEvanstonUSA
  3. 3.Saint Joseph Mercy HospitalAnn ArborUSA
  4. 4.Danbury HospitalDanburyUSA

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