Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer Genetics Group

Genetic testing for hereditary cancer predisposition has evolved rapidly in recent years with the discovery of new genes, but there is much debate over the clinical utility of testing genes for which there are currently limited data regarding the degree of associated cancer risk. To address the discrepancies that have arisen in the provision of these tests across the UK, the UK Cancer Genetics Group facilitated a 1-day workshop with representation from the majority of National Health Service (NHS) clinical genetics services. Using a preworkshop survey followed by focused discussion of genes without prior majority agreement for inclusion, we achieved consensus for panels of cancer genes with sufficient evidence for clinical utility, to be adopted by all NHS genetics services. To support consistency in the delivery of these tests and advice given to families across the country, we also developed management proposals for individuals who are found to have pathogenic mutations in these genes. However, we fully acknowledge that the decision regarding what test is most appropriate for an individual family rests with the clinician, and will depend on factors including specific phenotypic features and the family structure.

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Cancer Genetics Services in the UK

Disease Markers ◽

10.1155/1999/178217 ◽

1999 ◽

Vol 15 (1-3) ◽

pp. 44-45 ◽

Cited By ~ 1

Author(s):

Shirley V. Hodgson

Keyword(s):

Cancer Genetics ◽

Genetics Services ◽

The Uk

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A Key Role for the Genetic Counsellor in the Genomics Era

F1000Research ◽

10.12688/f1000research.14222.2 ◽

2018 ◽

Vol 7 ◽

pp. 420

Author(s):

Flora M. Joseph

Keyword(s):

Genetic Testing ◽

Exome Sequencing ◽

Clinical Genetics ◽

Genetic Counsellor ◽

Diagnostic Potential ◽

Whole Exome ◽

Genetics Services ◽

Testing Techniques ◽

Clinical Genetics Services ◽

The Uk

New genetic testing technologies such as microarrays and whole exome sequencing mean the diagnostic potential for a child with a development disorder is greatly increased over traditional testing techniques. With this increased potential comes increased expectations from families and professionals about the answers a diagnosis will provide. However, limitations remain and a proportion of individuals will continue to remain undiagnosed. In addition, some individuals will receive novel or very rare diagnoses about which very little is known in terms of prognosis and effective treatments. In this paper, I present an argument for why these families would benefit from additional Genetic Counsellor support and how Clinical Genetics services in the UK could provide this support. I acknowledge that resources are limited, but as demands on services increase and interactions with families become shorter, I argue that this kind of service should be prioritised, for the benefit of these families.

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The possible implications of advances in genetic testing technologies for Genetic Counsellors working with families of children with developmental disorders

F1000Research ◽

10.12688/f1000research.14222.1 ◽

2018 ◽

Vol 7 ◽

pp. 420

Author(s):

Flora M. Joseph

Keyword(s):

Genetic Testing ◽

Developmental Disorders ◽

Clinical Genetics ◽

Genetic Counsellor ◽

Diagnostic Potential ◽

Whole Exome ◽

Genetics Services ◽

Testing Techniques ◽

Clinical Genetics Services ◽

The Uk

New genetic testing technologies such as microarrays and whole exome sequencing mean the diagnostic potential for a child with a development disorder is greatly increased over traditional testing techniques. With this increased potential comes increased expectations from families and professionals about the answers a diagnosis will provide. However, limitations remain and a proportion of individuals will continue to remain undiagnosed. In addition, some individuals will receive novel or very rare diagnoses about which very little is known in terms of prognosis and effective treatments. In this paper, I present an argument for why these families would benefit from additional Genetic Counsellor support and how Clinical Genetics services in the UK could provide this support. I acknowledge that resources are limited, but as demands on services increase and interactions with families become shorter, I argue that these resources should be fought for, for the benefit of these families.

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Outcomes of retesting BRCA-negative patients using multigene panels.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.23 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 23-23 ◽

Cited By ~ 3

Author(s):

Siddhartha Yadav ◽

Jennifer Fulbright ◽

Heidi Dreyfuss ◽

Ashley Reeves ◽

Sarah Campian ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

New Technologies ◽

Cancer Genetics ◽

Pathogenic Mutation ◽

Cancer Genes ◽

Panel Testing ◽

New Genes ◽

Pathogenic Mutations ◽

Potential Clinical Benefit

23 Background: New technologies for identifying hereditary predisposition to breast cancer have led to the discovery of novel genes associated with cancer risk. This has prompted re-evaluation of patients who previously tested negative for BRCA1/2 gene mutations, with a possibility of discovering new genes which may impact management. This study reports on the results of retesting patients who previously were negative for BRCA1/2. Methods: Patients who tested negative for BRCA1/2 mutations who had significant personal and family history were referred back to the Cancer Genetics Center between February 1, 2012 and May 30, 2105 for discussion of additional testing. A detailed personal and family history was reviewed, and patients were counseled about the genetics and clinical implications of panel testing for multiple breast cancer genes. Panel testing using next generation sequencing technologies was ordered. Patients were seen in follow up for discussion of results and management. Results: A total of 12 pathogenic mutations were identified during the study period. The genes and frequencies of these mutations were: CHEK2(3), PALB2(3), ATM(2), APC(1), BARD(1), CDH(1), MUTYH(1). There were 33 variants of undetermined significance(VUS) in 27 patients. 5 of these were seen in patients with a known pathogenic mutation; 3 others were later classified as benign. The frequencies of these VUSs were: ATM (9), PALB2(3), BARD1 (3), PTEN(3), PMS2(3), MSH6(2), CHEK2 (1), MYH(1), RAD51(1), BRIP1(2), NF1(1), BMPR1A(1). Of the 46 patients who had their initial BRCA testing and repeat panel testing between February 1, 2012 and May 30, 2015, 6 (13%) tested positive for a pathogenic mutation. Conclusions: This study demonstrates the feasibility and potential clinical benefit of retesting individuals who previously tested negative for BRCA1/2 mutation. This approach had a significant management impact on patients and their families, with a 13% detection rate of pathogenic mutations. The success of retesting is predicated upon an infrastructure of provider and patient education, pre and post genetic counseling and serves as a model for other centers.

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UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants

Journal of Medical Genetics ◽

10.1136/jmedgenet-2020-106876 ◽

2020 ◽

pp. jmedgenet-2020-106876 ◽

Cited By ~ 3

Author(s):

Helen Hanson ◽

Angela F Brady ◽

Gillian Crawford ◽

Rosalind A Eeles ◽

Sarah Gibson ◽

...

Keyword(s):

Patient Group ◽

Cancer Genetics ◽

Wide Spectrum ◽

Brain Mri ◽

Breast Mri ◽

Whole Body ◽

Clinical Genetics ◽

Pathogenic Variants ◽

Surveillance Protocol ◽

The Uk

Constitutional pathogenic variants in TP53 are associated with Li-Fraumeni syndrome or the more recently described heritable TP53-related cancer syndrome and are associated with increased lifetime risks of a wide spectrum of cancers. Due to the broad tumour spectrum, surveillance for this patient group has been limited. To date, the only recommendation in the UK has been for annual breast MRI in women; however, more recently, a more intensive surveillance protocol including whole-body MRI (WB-MRI) has been recommended by International Expert Groups. To address the gap in surveillance for this patient group in the UK, the UK Cancer Genetics Group facilitated a 1-day consensus meeting to discuss a protocol for the UK. Using a preworkshop survey followed by structured discussion on the day, we achieved consensus for a UK surveillance protocol for TP53 carriers to be adopted by UK Clinical Genetics services. The key recommendations are for annual WB-MRI and dedicated brain MRI from birth, annual breast MRI from 20 years in women and three-four monthly abdominal ultrasound in children along with review in a dedicated clinic.

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Patient advice and reference

Endocrinology (Oxford Desk Reference) ◽

10.1093/med/9780199672837.003.0019 ◽

2018 ◽

pp. 467-479

Author(s):

Helen E. Turner ◽

Richard Eastell ◽

Ashley Grossman

Keyword(s):

Genetic Testing ◽

Genetic Counselling ◽

Mineral Metabolism ◽

Genetic Disorder ◽

Clinical Genetics ◽

Patient Support ◽

Genetics Services ◽

Clinical Genetics Services ◽

Patient Advice ◽

The Uk

This chapter provides simplified figures and diagrams to help explain common hormonal conditions to patients in clinic, as well as resources on bone and mineral metabolism, such as the National Osteoporosis Society (commonly abbreviated as NOS) in the UK. It discusses clinical genetics services, including genetic testing and genetic counselling, which is defined as ‘a communications process which deals with human problems associated with the occurrence, or the risk of occurrence, of a genetic disorder in a family’. The chapter also provides information on resources for travel advice and other forms of patient support. In addition, it enumerates services offered to better understand endocrine-related disorders, testing options, education materials, and treatments.

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Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-021-00176-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lucie G. Hallenstein ◽

Carol Sorensen ◽

Lorraine Hodgson ◽

Shelly Wen ◽

Justin Westhuyzen ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cancer Genetics ◽

Eligibility Criteria ◽

Pathogenic Variants ◽

Genetics Services ◽

Age Of Diagnosis ◽

Over Time

Abstract Background Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014–2018. Methods Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. Results There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014–2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. Conclusions Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

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