Determining the clinical validity of hereditary colorectal cancer and polyposis susceptibility genes using the Clinical Genome Resource Clinical Validity Framework

Seifert, Bryce A.; McGlaughon, Jennifer; Jackson, Sarah; Ritter, Deborah; Roberts, Maegan E.; Schmidt, Ryan; Thompson, Bryony A.; Jimenez, Sharisse; Trapp, Mackenzie; Lee, Kristy; Plon, Sharon E.; Offit, Kenneth; Stadler, Zsofia K.; Zhang, Liying; Greenblatt, Marc S.; Ferber, Matthew J.

doi:10.1038/s41436-018-0373-1

Cited by 21 publications

(27 citation statements)

References 28 publications

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“…A number of different multigene panel tests, including those assessing hereditary cancer syndrome risk, cardiac and thoracic condition diagnosis, and underlying causes of hearing loss, have been evaluated by application of the ClinGen clinical validity framework (DiStefano et al, 2019; Ingles et al, 2019; Lee et al, 2019; Renard et al, 2018; Seifert et al, 2019). The ability of the ClinGen framework to be applied in an evidence‐based and systematic manner in many different disease areas is a testament to its strength as a tool for clinical validity assessment of monogenic conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The ClinGen gene‐disease association framework has been applied in a number of disease‐specific areas to determine the clinical validity of genes included on panels (DiStefano et al, 2019; Hosseini et al, 2018; Ingles et al, 2019; Lee et al, 2019; McGlaughon et al, 2019; Renard et al, 2018; Seifert et al, 2019). For example, of 21 genes included on panels assessing single‐gene causes of Brugada syndrome, an arrhythmia condition that increases risk for sudden cardiac death, only one gene ( SCN5A ) was classified as having Definitive evidence of clinical validity, while the remaining 20 were classified as Disputed (Hosseini et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Clinical validity of expanded carrier screening: Evaluating the gene‐disease relationship in more than 200 conditions

et al. 2020

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Clinical guidelines consider expanded carrier screening (ECS) to be an acceptable method of carrier screening. However, broader guideline support and payer adoption require evidence for associations between the genes on ECS panels and the conditions for which they aim to identify carriers. We applied a standardized framework for evaluation of gene‐disease association to assess the clinical validity of conditions screened by ECS panels. The Clinical Genome Resource (ClinGen) gene curation framework was used to assess genetic and experimental evidence of associations between 208 genes and conditions screened on two commercial ECS panels. Twenty‐one conditions were previously classified by ClinGen, and the remaining 187 were evaluated by curation teams at two laboratories. To ensure consistent application of the framework across the laboratories, concordance was evaluated on a subset of conditions. All 208 evaluated conditions met the evidence threshold for supporting a gene‐disease association. Furthermore, 203 of 208 (98%) achieved the strongest (“Definitive”) level of gene‐disease association. All conditions evaluated by both commercial laboratories were similarly classified. Assessment using the ClinGen standardized framework revealed strong evidence of gene‐disease association for conditions on two ECS panels. This result establishes the disease‐level clinical validity of the panels considered herein.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical validity of expanded carrier screening: Evaluating the gene‐disease relationship in more than 200 conditions

et al. 2020

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“…Although a batch of genes considered clinically actionable with quantified magnitude of risk are present in virtually all panels, there is a significant amount of genes that lack comprehensive validation or have less evidence of association with CRC/polyposis and consequently minimal clinical utility, that are included in many multigene panels. In fact, recent data from the ClinGen Clinical Validity framework show that < 60% of the genes on clinically available panels have strong or definitive evidence of association with hereditary colorectal cancer or polyposis, and > 40% have only moderate, limited, disputed, or refuted evidence [54].…”

Section: Multigene Panel Testing In Familial Crcmentioning

confidence: 99%

“…For the current guidelines, we have reviewed the available information from reputable sources with expert panels to define strength of evidence and evaluate the clinical utility of genes associated with CRC and polyposis. Therefore, we considered the following sources: (i) the NCCN Guidelines for colorectal cancer v1.2019 [53], (ii) ClinGen Clinical Validity framework [54] and (iii) Lorans et al's review [55]. The applied criteria to evaluate the level of validation are slightly different among them with some discordant results.…”

Section: Multigene Panel Testing In Familial Crcmentioning

confidence: 99%

SEOM clinical guideline on hereditary colorectal cancer (2019)

et al. 2020

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In the last 2 decades, clinical genetics on hereditary colorectal syndromes has shifted from just a molecular characterization of the different syndromes to the estimation of the individual risk of cancer and appropriate risk reduction strategies. In the last years, new specific therapies for some subgroups of patients have emerged as very effective alternatives. At the same time, germline multigene panel testing by next-generation sequencing (NGS) technology has become the new gold standard for molecular genetics.

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“…Capalbo et al [114] , 2019 Wang et al [115] , 2018 Gao et al [116] , 2019 Seifert et al [117] , 2019…”

Section: Fbxw7 Braf Smad4 Met Fgfr1mentioning

confidence: 99%

Precision medicine for gastrointestinal cancer: Recent progress and future perspective

Matsuoka

Yashiro

2019

WJGO

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Gastrointestinal (GI) cancer has a high tumor incidence and mortality rate worldwide. Despite significant improvements in radiotherapy, chemotherapy, and targeted therapy for GI cancer over the last decade, GI cancer is characterized by high recurrence rates and a dismal prognosis. There is an urgent need for new diagnostic and therapeutic approaches. Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer. Here we review the application and status of precision medicine in GI cancer. Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy. With the introduction of gene panels including next-generation sequencing, it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer. Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors, novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs. These progressions will make it feasible to incorporate clinical, genome-based, and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.

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Determining the clinical validity of hereditary colorectal cancer and polyposis susceptibility genes using the Clinical Genome Resource Clinical Validity Framework

Cited by 21 publications

References 28 publications

Clinical validity of expanded carrier screening: Evaluating the gene‐disease relationship in more than 200 conditions

Clinical validity of expanded carrier screening: Evaluating the gene‐disease relationship in more than 200 conditions

SEOM clinical guideline on hereditary colorectal cancer (2019)

Precision medicine for gastrointestinal cancer: Recent progress and future perspective

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