Couples coping with screening burden and diagnostic uncertainty in Li-Fraumeni syndrome: Connection versus independence

Young, Jennifer L.; Pantaleao, Ashley; Zaspel, Lori; Bayer, Jessica; Peters, June A.; Khincha, Payal P.; Bremer, Renee; Loud, Jennifer T.; Greene, Mark H.; Achatz, Maria Isabel; Savage, Sharon A.; Werner‐Lin, Allison

doi:10.1080/07347332.2018.1543376

Cited by 21 publications

(24 citation statements)

References 28 publications

(26 reference statements)

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“…variants (Batalini et al, 2019;Fortuno, James, & Spurdle, 2018), and cancer surveillance for people with TP53 pathogenic germline variants is time intensive and emotionally stressful (Ballinger et al, 2017;Kratz et al, 2017;Pantaleao et al, 2019;Villani et al, 2016;Young et al, 2019). Therefore, robust TP53 variant classification is essential for optimal clinical care.…”

Section: Discussionmentioning

confidence: 99%

“…This has led to an increased number of variants of uncertain significance identified in TP53, including in cancer patients who do not meet LFS criteria, and individuals without cancer (Bittar et al, 2019). Given the significant clinical and emotional challenges that come with an LFS diagnosis (Ballinger et al, 2017;Evans et al, 2006;Kratz et al, 2017;Schon & Tischkowitz, 2018;Villani et al, 2016;Young et al, 2019), it is essential to correctly assign TP53 germline variant pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

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Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants

et al. 2020

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Germline pathogenic variants in TP53 are associated with Li‐Fraumeni syndrome, a cancer predisposition disorder inherited in an autosomal dominant pattern associated with a high risk of malignancy, including early‐onset breast cancers, sarcomas, adrenocortical carcinomas, and brain tumors. Intense cancer surveillance for individuals with TP53 germline pathogenic variants is associated with reduced cancer‐related mortality. Accurate and consistent classification of germline variants across clinical and research laboratories is important to ensure appropriate cancer surveillance recommendations. Here, we describe the work performed by the Clinical Genome Resource TP53 Variant Curation Expert Panel (ClinGen TP53 VCEP) focused on specifying the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification to the TP53 gene. Specifications were developed for 20 ACMG/AMP criteria, while nine were deemed not applicable. The original strength level for the 10 criteria was also adjusted due to current evidence. Use of TP53‐specific guidelines and sharing of clinical data among experts and clinical laboratories led to a decrease in variants of uncertain significance from 28% to 12% compared with the original guidelines. The ClinGen TP53 VCEP recommends the use of these TP53‐specific ACMG/AMP guidelines as the standard strategy for TP53 germline variant classification.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants

et al. 2020

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“…The task of the TP53 VCEP was to specify the ACMG/AMP guidelines to assist with the clinical classification of variants in the TP53 gene. There is a rapidly growing number of individuals without personal or family history consistent with LFS who have germline TP53 variants (Batalini et al, 2019; Fortuno, James, & Spurdle, 2018), and cancer surveillance for people with TP53 pathogenic germline variants is time intensive and emotionally stressful (Ballinger et al, 2017; Kratz et al, 2017; Pantaleao et al, 2019; Villani et al, 2016; Young et al, 2019). Therefore, robust TP53 variant classification is essential for optimal clinical care.…”

Section: Discussionmentioning

confidence: 99%

“…This has led to an increased number of variants of uncertain significance identified in TP53 , including in cancer patients who do not meet LFS criteria, and individuals without cancer (Bittar et al, 2019). Given the significant clinical and emotional challenges that come with an LFS diagnosis (Ballinger et al, 2017; Evans et al, 2006; Kratz et al, 2017; Schon & Tischkowitz, 2018; Villani et al, 2016; Young et al, 2019), it is essential to correctly assign TP53 germline variant pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants

Fortuño

Lee

Olivier

et al. 2020

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Germline pathogenic variants in TP53 are associated with Li-Fraumeni syndrome (LFS), an autosomal dominant cancer predisposition disorder associated with high risk of malignancy, including early onset breast cancers, sarcomas, adrenocortical carcinomas and brain tumors. Intense cancer surveillance for individuals with TP53 germline pathogenic variants has been shown to decrease mortality; therefore, accurate and consistent classification of variants across clinical and research laboratories is crucial to patient care. Here, we describe the work performed by the Clinical Genome Resource TP53 Variant Curation Expert Panel (ClinGen TP53 VCEP) focused on specifying the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification to the TP53 gene. Specifications were applied to twenty ACMG/AMP criteria while nine were deemed not applicable. The original strength level for ten criteria was also adjusted due to current evidence. Use of the TP53-specific guidelines and sharing of clinical data amongst experts and clinical laboratories led to a decrease in variants of uncertain significance from 28% to 12% in comparison with the original guidelines. The ClinGen TP53 VCEP recommends the use of these TP53-specific ACMG/AMP guidelines as the standard strategy for TP53 germline variant classification.

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“…Prior research has begun to illuminate the psychosocial effects on families living with LFS (Forbes Shepherd et al, 2018), but no specific patterns have emerged in which family members share the burden of cancer screening and risk management that providers can encourage in the families with whom they work (Peters et al, 2016; Ross et al, 2017). Recent literature regarding family coping with hereditary cancer stressors has reported that relatives often shift roles to meet new challenges; for example, members of a couple alternating leadership burdens or providing emotional support for the other’s distress related to LFS (Coyne et al, 2012; Young et al, 2018). The present study indicated that while one member filled a health leader role, others were sensitive to the demands that role placed on the individual and often offered support or even shifted into that role.…”

Section: Discussionmentioning

confidence: 99%

Family Health Leaders: Lessons on Living with Li‐Fraumeni Syndrome across Generations

et al. 2019

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Li-Fraumeni Syndrome (LFS) is a hereditary disorder that confers an approximately 90% lifetime risk of cancer and requires comprehensive lifetime cancer screening. We explored healthcare roles for managing LFS-related cancer risks and treatments that were assumed by parents, adolescents, and adult children. Semi-structured interviews were conducted with 23 families. Family groupings were comprised of 2-5 members, with the younger generation in each family ranging in age from 7 to 40 years. Using grounded theory methods, we conducted open and focused coding of interview transcript content. Family members described how the role of health leader was implemented in their family, as well as factors such as maturation of a child or death of a member that determined who assumed particular roles and how these roles shifted over time. They often expressed collective responsibility for helping relatives understand LFS and implement appropriate cancer risk management. Members demonstrated their health role by attending others' medical appointments for support or information gathering. The health leader role was intergenerational and provided the family necessary support in navigating complicated healthcare decisions. Our findings provide insight into healthcare providers regarding how LFS patients and their relatives develop unique medical decision-making and caring roles influenced by the hereditary nature of LFS, and how these roles change over time. Providers who are attuned to family role dynamics may be better able to meet relatives' psychosocial and medical needs by understanding how living with LFS influences the family system's functioning and facilitating members' support for each other.

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Couples coping with screening burden and diagnostic uncertainty in Li-Fraumeni syndrome: Connection versus independence

Cited by 21 publications

References 28 publications

Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants

Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants

Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants

Family Health Leaders: Lessons on Living with Li‐Fraumeni Syndrome across Generations

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