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. 2018 Oct;17(4):495-505.
doi: 10.1007/s10689-018-0070-x.

Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk

Allison H West  1 , Kathleen R Blazer  2 , Jessica Stoll  3   4 , Matthew Jones  5 , Caroline M Weipert  3 , Sarah M Nielsen  3 , Sonia S Kupfer  3   5 , Jeffrey N Weitzel  2 , Olufunmilayo I Olopade  6   7
Affiliations

Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk

Allison H West et al. Fam Cancer. 2018 Oct.

Abstract

Comprehensive genomic cancer risk assessment (GCRA) helps patients, family members, and providers make informed choices about cancer screening, surgical and chemotherapeutic risk reduction, and genetically targeted cancer therapies. The increasing availability of multigene panel tests for clinical applications allows testing of well-defined high-risk genes, as well as moderate-risk genes, for which the penetrance and spectrum of cancer risk are less well characterized. Moderate-risk genes are defined as genes that, when altered by a pathogenic variant, confer a 2 to fivefold relative risk of cancer. Two such genes included on many comprehensive cancer panels are the DNA repair genes ATM and CHEK2, best known for moderately increased risk of breast cancer development. However, the impact of screening and preventative interventions and spectrum of cancer risk beyond breast cancer associated with ATM and/or CHEK2 variants remain less well characterized. We convened a large, multidisciplinary, cross-sectional panel of GCRA clinicians to review challenging, peer-submitted cases of patients identified with ATM or CHEK2 variants. This paper summarizes the inter-professional case discussion and recommendations generated during the session, the level of concordance with respect to recommendations between the academic and community clinician participants for each case, and potential barriers to implementing recommended care in various practice settings.

Keywords: ATM; CHEK2; Cancer genetics; Genomic cancer risk assessment (GCRA); Moderate-risk gene; Panel test.

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Conflict of interest statement

Conflict of interest: Dr. Olufunmilayo Olopade is co-founder of CancerIQ. All co-authors declare that they have no conflict of interest

Figures

Fig. 1
Fig. 1
Case 1: ATM Carrier Seeking Risk-Reducing Mastectomy. Unknown, cancer of unknown type. Breast, breast cancer. Please see associated vignette for more details
Fig. 2
Fig. 2
Case 2: Pancreatic Cancer Risk for ATM Carriers – True or Unrelated? Pancreas, pancreas cancer; Endometrial, endometrial cancer; Kidney, kidney cancer; Breast, breast cancer. Please see associated vignette for more details
Fig. 3
Fig. 3
Case 3: Is radiation treatment contra-indicated in a carrier of homozygous ATM variants of uncertain significance? Lung, lung cancer; Breast, breast cancer. Please see associated vignette for more details.
Fig 4
Fig 4
Case 4: Prioritizing Genetic Testing in Time Sensitive Situations. Breast, breast cancer; DCIS, ductal carcinoma in situ; Liver, liver cancer. Please see associated vignette for more details
Fig. 5
Fig. 5
Case 5: Spectrum of Screening for CHEK2 Carriers. Colon, colorectal cancer; Prostate, prostate cancer; Breast, breast cancer. Please see associated vignette for more details
See this image and copyright information in PMC

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References

    1. Hodgson SV. A Practical Guide to Human Cancer Genetics. Third. New York: Cambridge University Press; 2007.
    1. Lindor NM, McMaster ML, Lindor CJ, Greene MH. Concise handbook of familial cancer susceptibility syndromes - second edition. J Natl Cancer Inst Monogr. 2008;38:1–93. doi: 10.1093/jncimonographs/lgn001. - DOI - PubMed
    1. Offit K. Clinical Cancer Genetics: Risk Counseling and Management New York. New York: Wiley Liss; 1998.
    1. Weitzel JN, Blazer KR, MacDonald DJ, Culver JO, Offit K. Genetics, genomics, and cancer risk assessment: State of the Art and Future Directions in the Era of Personalized Medicine. CA Cancer J Clin. 2011;61(5):327–59. doi: 10.3322/caac.20128. - DOI - PMC - PubMed
    1. DeMarco TA, Smith KL, Nusbaum RH, Peshkin BN, Schwartz MD, Isaacs C. Practical aspects of delivering hereditary cancer risk counseling. Semin Oncol. 2007;34(5):369–78. doi: 10.1053/j.seminoncol.2007.07.003. - DOI - PubMed

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