Mainstreaming genetic testing of cancer predisposition genes

Rahman, Nazneen

doi:10.7861/clinmedicine.14-4-436

Cited by 76 publications

(71 citation statements)

References 19 publications

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“…Given the growing demand for genomic testing and the limited capacity of specialist clinical genetics departments it is broadly recognised that integration of genomics into mainstream specialties and the development of clinical expertise will be essential 9. However, implementation of scientific advances is recognised to be slow at the best of times and in genomics particular barriers exist: genomics is often regarded as a complex subject; while its implementation will take place across all specialties, until very recently it has largely been regarded as relevant only to rare disorders and subspecialists or clinical geneticists rather than those in mainstream areas of practice 3 10…”

Section: Are Clinicians Ready To Implement Genomic Medicine?mentioning

confidence: 99%

Preparing clinicians for genomic medicine

Slade

Burton

2016

Postgraduate Medical Journal

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Section: Are Clinicians Ready To Implement Genomic Medicine?mentioning

confidence: 99%

Preparing clinicians for genomic medicine

Slade

Burton

2016

Postgraduate Medical Journal

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“…23 Several technical questions also remain about these new tests. NGS has traditionally had analytical limitations 24 compared with established technologies, such as Sanger sequencing, 25 quantitative PCR, 26 multiplex ligationdependent probe amplification, 27 and copy number microarrays.…”

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confidence: 98%

A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients

Lincoln

Kobayashi

Anderson

et al. 2015

The Journal of Molecular Diagnostics

181

169

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Gene panels for hereditary breast and ovarian cancer risk assessment are gaining acceptance, even though the clinical utility of these panels is not yet fully defined. Technical questions remain, however, about the performance and clinical interpretation of gene panels in comparison with traditional tests. We tested 1105 individuals using a 29-gene next-generation sequencing panel and observed 100% analytical concordance with traditional and reference data on >750 comparable variants. These 750 variants included technically challenging classes of sequence and copy number variation that together represent a significant fraction (13.4%) of the pathogenic variants observed. For BRCA1 and BRCA2, we also compared variant interpretations in traditional reports to those produced using only non-proprietary resources and following criteria based on recent (2015) guidelines. We observed 99.8% net report concordance, albeit with a slightly higher variant of uncertain significance rate. In 4.5% of BRCA-negative cases, we uncovered pathogenic variants in other genes, which appear clinically relevant. Previously unseen variants requiring interpretation accumulated rapidly, even after 1000 individuals had been tested. We conclude that next-generation sequencing panel testing can provide results highly comparable to traditional testing and can uncover potentially actionable findings that may be otherwise missed. Challenges remain for the broad adoption of panel tests, some of which will be addressed by the accumulation of large public databases of annotated clinical variants.

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“…Genetic testing for pediatric oncology patients is rapidly becoming a standard of care, and yet many clinicians are unclear about who would benefit, and currently, few guidelines outline referral criteria 1,5 . To address that gap, studies have advocated for the addition of genetic counselling to routine care in pediatric oncology follow-up clinics.…”

Section: Introductionmentioning

confidence: 99%

“…Many families want to know why their child developed cancer and are concerned about the risk for their other children. Genetic testing that identifies a hereditary cancer predisposition syndrome not only answers both of those questions, but is also important to establish the proper management, screening, and risk counselling for other family members 1,4 . Conversely, genetic testing that does not identify a pathogenic variant could reassure families that the risk of malignancy is low for siblings, although it does not rule risk entirely out.…”

Section: Introductionmentioning

confidence: 99%

“…More than 100 cancer predisposition genes have been shown to increase the risk of cancer 1 , and up to 10% of pediatric oncology patients are thought to harbour a germline mutation 2 . Advances in sequencing technology have made clinical genetic testing widely available, and large gene panels can be used to test multiple genes concurrently 3 .…”

Section: Introductionmentioning

confidence: 99%

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Using Family History Forms in Pediatric Oncology to Identify Patients for Genetic Assessment

et al. 2017

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ObjectiveWe set out to identify and offer genetic testing to the 5%-10% of pediatric cancer patients who have been estimated to carry germline mutations in inherited cancer predisposition syndromes. Clinical genetic testing has become widely available, and thus in busy oncology clinics, tools are needed to identify patients who could benefit from a referral to genetics. MethodsWe studied the clinical utility of administering a family history form in the pediatric oncology long-term follow-up clinic to identify patients who might have an inherited cancer predisposition syndrome. Genetic testing involved primarily Sanger sequencing in clia (Clinical Laboratory Improvement Amendments)-certified laboratories. ResultsOf 57 patients who completed forms, 19 (33.3%) met criteria for referral to genetics. A significant family history of cancer was present for 4 patients, and 12 patients underwent genetic testing. Of 18 genetic tests ordered, none identified a pathogenic mutation, likely because of a small sample size and a candidate-gene approach to testing. Three families were also identified for further assessment based on a family history of breast cancer, with two of families having members eligible for BRCA1 and BRCA2 testing.Conclusions Genetic testing in pediatric oncology patients is important to guide the management of patients who have an inherited cancer predisposition syndrome and to identify other family members at risk when mutations are identified. When no mutations are identified, that information is often reassuring to families who are worried about siblings. However, in the absence of an identified genetic cause in a patient, some uncertainty remains.

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Mainstreaming genetic testing of cancer predisposition genes

Abstract: Referrals are invited from consultants in secondary and/or tertiary care for patients in whom the diagnosis of EDS is suspected but not confirmed for one of the following reasons:

Cited by 76 publications

References 19 publications

Preparing clinicians for genomic medicine

Preparing clinicians for genomic medicine

A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients

Using Family History Forms in Pediatric Oncology to Identify Patients for Genetic Assessment

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