Managing Patient with Mutations in PALB2, CHEK2, or ATM

Acevedo, Francisco; Deng, Zhengyi; Armengol, Victor Diego; Hughes, Kevin S.

doi:10.1007/s12609-018-0269-8

Cited by 2 publications

(1 citation statement)

References 48 publications

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“…Although many of the genes analyzed in the 67-gene panel are currently not actionable per NCCN Guidelines, there are still a number that are outside the spectrum of testing but may influence screening and management. For instance, while CHEK2, ATM , and PALB2 are less penetrant than BRCA1 and BRCA2 , they are considered moderate risk and increased screening may be considered ( Acevedo et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Current Testing Guidelines: A Retrospective Analysis of a Community-Based Hereditary Cancer Program

Ward

Elder

Habtemariam

2021

JADPRO

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It is estimated that 5% to 10% of all cancers are related to a hereditary cancer syndrome. However, specific cancers, such as pancreatic and ovarian cancers, are related to hereditary cancer syndromes 15% to 20% of the time. Genetic testing guidelines for hereditary cancer syndromes are frequently reviewed and updated by the National Comprehensive Cancer Network (NCCN). The purpose of this retrospective analysis is to identify carriers of pathogenic variants or hereditary cancer syndrome who do not meet NCCN criteria for testing and compare the results with previous studies. The data obtained can be used to provide recommendations to assess current guidelines for testing and evaluate the benefit of comprehensive panel testing vs. standard testing for specific hereditary cancer syndromes. This project is a retrospective review of clinical histories of patients who had multigene panel testing between September 2015 and February 2019 through a cancer outreach and risk assessment (CORA) program. Frequencies analyses were performed to analyze results. A total of 233 individuals were included in the analysis: 171 met BRCA1/2 testing criteria, 66 met Lynch syndrome criteria, and 4 met polyposis criteria. Of the individuals meeting established criteria for testing, 39 were identified with pathogenic variants. However, only 10 of these individuals were identified with a pathogenic variant associated with the criteria for which they met. Genetic testing that is limited to only those patients with genes associated with hereditary cancer syndromes may lead to exclusion of other potentially actionable genes, which may impair a patient’s ability to receive additional screening or preventative measures.

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Section: Discussionmentioning

confidence: 99%

Current Testing Guidelines: A Retrospective Analysis of a Community-Based Hereditary Cancer Program

Ward

Elder

Habtemariam

2021

JADPRO

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Bayesian meta-analysis of penetrance for cancer risk

Ruberu,

Braun,

Parmigiani

et al. 2024

Biometrics

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Multi-gene panel testing allows many cancer susceptibility genes to be tested quickly at a lower cost making such testing accessible to a broader population. Thus, more patients carrying pathogenic germline mutations in various cancer-susceptibility genes are being identified. This creates a great opportunity, as well as an urgent need, to counsel these patients about appropriate risk-reducing management strategies. Counseling hinges on accurate estimates of age-specific risks of developing various cancers associated with mutations in a specific gene, ie, penetrance estimation. We propose a meta-analysis approach based on a Bayesian hierarchical random-effects model to obtain penetrance estimates by integrating studies reporting different types of risk measures (eg, penetrance, relative risk, odds ratio) while accounting for the associated uncertainties. After estimating posterior distributions of the parameters via a Markov chain Monte Carlo algorithm, we estimate penetrance and credible intervals. We investigate the proposed method and compare with an existing approach via simulations based on studies reporting risks for two moderate-risk breast cancer susceptibility genes, ATM and PALB2. Our proposed method is far superior in terms of coverage probability of credible intervals and mean square error of estimates. Finally, we apply our method to estimate the penetrance of breast cancer among carriers of pathogenic mutations in the ATM gene.

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Managing Patient with Mutations in PALB2, CHEK2, or ATM

Cited by 2 publications

References 48 publications

Current Testing Guidelines: A Retrospective Analysis of a Community-Based Hereditary Cancer Program

Current Testing Guidelines: A Retrospective Analysis of a Community-Based Hereditary Cancer Program

Bayesian meta-analysis of penetrance for cancer risk

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