A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings.

Humans Genomics / methods Exome Sequencing Genome, Human Exome Base Sequence

Journal

Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873

Informations de publication

Date de publication:
Dec 2022
Historique:
received: 28 03 2022
accepted: 05 06 2022
pubmed: 24 6 2022
medline: 22 11 2022
entrez: 23 6 2022
Statut: ppublish

Résumé

Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in three phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative refinement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary (cancer) and secondary findings, with in-depth details of each finding generated from exome sequencing. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically significant SFs to patients and providers, facilitating clinical management of GS results.

Identifiants

DOI: 10.1007/s00439-022-02466-5 PMID: 35739291
pubmed: 35739291
doi: 10.1007/s00439-022-02466-5
pii: 10.1007/s00439-022-02466-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1875-1885

Subventions

Organisme : CIHR
ID : 143310
Pays : Canada
Organisme : CIHR
ID : 135730
Pays : Canada
Organisme : Canadian Cancer Society Research Institute
ID : 705665
Organisme : McLaughlin Centre
ID : MC-2012-13
Organisme : McLaughlin Family Foundation
ID : MC-2014-11-1
Organisme : CIHR
ID : 143310
Pays : Canada
Organisme : CIHR
ID : 135730
Pays : Canada

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

Adam MP, Ardinger HH, Pagon RA et al. (1993–2022) GeneReviews. University of Washington, Seattle
Bennette CS, Gallego CJ, Burke W, Jarvik GP, Veenstra DL (2015) The cost-effectiveness of returning incidental findings from next-generation genomic sequencing. Genet Med 17:587–595. https://doi.org/10.1038/gim.2014.156
doi: 10.1038/gim.2014.156 pubmed: 25394171
Bombard Y, Hayeems RZ (2021) How digital tools can advance quality and equity in genomic medicine. Nat Rev Genet 21:505–506. https://doi.org/10.1038/s41576-020-0260-x
doi: 10.1038/s41576-020-0260-x
Bombard Y, Clausen M, Shickh S et al (2020) Effectiveness of the genomics ADvISER decision aid for the selection of secondary findings from genomic sequencing: a randomized clinical trial. Genet Med 22:727–735. https://doi.org/10.1038/s41436-019-0702-z
doi: 10.1038/s41436-019-0702-z pubmed: 31822848
Dean L (2012) Warfarin therapy and VKORC1 and CYP genotype. In: Pratt VM, Scott SA, Pirmohamed M et al (eds) Medical genetics summaries [Internet]. National Center for Biotechnology Information, Bethesda, pp 613–625
Dorschner MO, Amendola LM, Shirts BH et al (2014) Refining the structure and content of clinical genomic reports. Am J Med Genet C Semin Med Genet 166C:85–92. https://doi.org/10.1002/ajmg.c.31395
doi: 10.1002/ajmg.c.31395 pubmed: 24616401
Facio FM, Eidem H, Fisher T et al (2013) Intentions to receive individual results from whole-genome sequencing among participants in the ClinSeq study. Eur J Hum Genet 21:261–265. https://doi.org/10.1038/ejhg.2012.179
doi: 10.1038/ejhg.2012.179 pubmed: 22892536
Fatumo S, Chikowore T, Choudhury A et al (2022) A roadmap to increase diversity in genomic studies. Nat Med 28:243–250. https://doi.org/10.1038/s41591-021-01672-4
doi: 10.1038/s41591-021-01672-4 pubmed: 35145307
Federici G, Soddu S (2020) Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers. J Exp Clin Cancer Res 39:46. https://doi.org/10.1186/s13046-020-01554-6
doi: 10.1186/s13046-020-01554-6 pubmed: 32127026 pmcid: 7055088
Franke A, McGovern DP, Barrett JC et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42:1118–1125. https://doi.org/10.1038/ng.717
doi: 10.1038/ng.717 pubmed: 21102463 pmcid: 3299551
Green RC, Berg JS, Grody WW et al (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 15:565–574. https://doi.org/10.1038/gim.2013.73
doi: 10.1038/gim.2013.73 pubmed: 23788249 pmcid: 3727274
Haga SB, Mills R, Pollak KI et al (2014) Developing patient-friendly genetic and genomic test reports: formats to promote patient engagement and understanding. Genome Med 6:58. https://doi.org/10.1186/s13073-014-0058-6
doi: 10.1186/s13073-014-0058-6 pubmed: 25473429 pmcid: 4254435
Hamosh A, Scott AF, Amberger J, Bocchini C, Valle D, McKusick VA (2002) Online Mendelian inheritance in man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res 30:52–55. https://doi.org/10.1093/nar/gki033
doi: 10.1093/nar/gki033 pubmed: 11752252 pmcid: 99152
Karczewski KJ, Francioli LC, Tiao G et al (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:434–443. https://doi.org/10.1038/s41586-020-2308-7
doi: 10.1038/s41586-020-2308-7 pubmed: 32461654 pmcid: 7334197
Landrum MJ, Lee JM, Riley GR et al (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42:D980-985. https://doi.org/10.1093/nar/gkt1113
doi: 10.1093/nar/gkt1113 pubmed: 24234437
McLaughlin HM, Ceyhan-Birsoy O, Christensen KD (2014) A systematic approach to the reporting of medically relevant findings from whole genome sequencing. BMC Med Genet 15:134. https://doi.org/10.1186/s12881-014-0134-1
doi: 10.1186/s12881-014-0134-1 pubmed: 25714468 pmcid: 4342199
Mighton C, Carlsson L, Clausen M et al (2019) Development of patient “profiles” to tailor counseling for incidental genomic sequencing results. Eur J Hum Genet 27:1008–1017. https://doi.org/10.1038/s41431-019-0352-2
doi: 10.1038/s41431-019-0352-2 pubmed: 30846854 pmcid: 6777527
Mighton C, Carlsson L, Clausen M et al (2020) Quality of life drives patients’ preferences for secondary findings from genomic sequencing. Eur J Hum Genet 28:1178–1186. https://doi.org/10.1038/s41431-020-0640-x
doi: 10.1038/s41431-020-0640-x pubmed: 32424322 pmcid: 7609335
Miller N, Lacroix EM, Backus JE (2000) MEDLINEplus: building and maintaining the national library of medicine’s consumer health web service. Bull Med Libr Assoc 88:11–17
pubmed: 10658959 pmcid: 35193
Miller DT, Lee K, Chung WK et al (2021) ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American college of medical genetics and genomics (ACMG). Genet Med 23:1381–1390. https://doi.org/10.1038/s41436-021-01172-3
doi: 10.1038/s41436-021-01172-3 pubmed: 34012068
O’Leary NA, Wright MW, Brister JR et al (2016) Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res 44:D733–D745. https://doi.org/10.1093/nar/gkv1189
doi: 10.1093/nar/gkv1189 pubmed: 26553804
Popejoy AB, Fullerton SM (2016) Genomics is failing on diversity. Nature 538:161–164. https://doi.org/10.1038/538161a
doi: 10.1038/538161a pubmed: 27734877 pmcid: 5089703
Reble E, Gutierrez Salazar M, Zakoor KR et al (2021) Beyond medically actionable results: an analytical pipeline for decreasing the burden of returning all clinically significant secondary findings. Hum Genet 140:493–504. https://doi.org/10.1007/s00439-020-02220-9
doi: 10.1007/s00439-020-02220-9 pubmed: 32892247
Recchia G, Chiappi A, Chandratillake G, Raymond L, Freeman ALJ (2020) Creating genetic reports that are understood by nonspecialists: a case study. Genet Med 22:353–361. https://doi.org/10.1038/s41436-019-0649-0
doi: 10.1038/s41436-019-0649-0 pubmed: 31506646
Rehm HL, Bale SJ, Bayrak-Toydemir P et al (2013) ACMG clinical laboratory standards for next-generation sequencing. Genet Med 15:733–747. https://doi.org/10.1038/gim.2013.92
doi: 10.1038/gim.2013.92 pubmed: 23887774 pmcid: 4098820
Rehm HL, Berg JS, Brooks LD et al (2015) ClinGen–the clinical genome resource. N Engl J Med 372:2235–2242. https://doi.org/10.1056/NEJMsr1406261
doi: 10.1056/NEJMsr1406261 pubmed: 26014595 pmcid: 4474187
Relling MV, Klein TE (2011) CPIC: clinical pharmacogenetics implementation consortium of the pharmacogenomics research network. Clin Pharm Ther 89:464–470. https://doi.org/10.1038/clpt.2010.279
doi: 10.1038/clpt.2010.279
Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med 17:405–424. https://doi.org/10.1038/gim.2015.30
doi: 10.1038/gim.2015.30 pubmed: 25741868 pmcid: 4544753
Sebastian A, Carroll JC, Vanstone M et al (2021) Widening the lens of actionability: a qualitative study of primary care providers’ views and experiences of managing secondary genomic findings. Eur J Hum Genet. https://doi.org/10.1038/s41431-021-00876-z (Epub ahead of print)
doi: 10.1038/s41431-021-00876-z pubmed: 33776058
Sebastian A, Carroll JC, Vanstone M et al (2022) Challenges and practical solutions for managing secondary genomic findings in primary care. Eur J Med Genet 65:104384. https://doi.org/10.1016/j.ejmg.2021.104384
doi: 10.1016/j.ejmg.2021.104384 pubmed: 34768014
Shickh S, Clausen M, Mighton C et al (2019) Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial. BMJ Open 9:e031092. https://doi.org/10.1136/bmjopen-2019-031092
doi: 10.1136/bmjopen-2019-031092 pubmed: 31594892 pmcid: 6797333
Shickh S, Mighton C, Uleryk E, Pechlivanoglou P, Bombard Y (2021) The clinical utility of exome and genome sequencing across clinical indications: a systematic review. Hum Genet 140:1403–1416. https://doi.org/10.1007/s00439-021-02331-x
doi: 10.1007/s00439-021-02331-x pubmed: 34368901
Solomon BD, Nguyen AD, Bear KA, Wolfsberg TG (2013) Clinical genomic database. Proc Natl Acad Sci USA 110:9851–9855. https://doi.org/10.1073/pnas.1302575110
doi: 10.1073/pnas.1302575110 pubmed: 23696674 pmcid: 3683745
Stark Z, Dolman L, Manolio TA et al (2019) Integrating genomics into healthcare: a global responsibility. Am J Hum Genet 104:13–20. https://doi.org/10.1016/j.ajhg.2018.11.014
doi: 10.1016/j.ajhg.2018.11.014 pubmed: 30609404 pmcid: 6323624
Suwinski P, Ong C, Ling MHT, Poh YM, Khan AM, Ong HS (2019) Advancing personalized medicine through the application of whole exome sequencing and big data analytics. Front Genet 10:49. https://doi.org/10.3389/fgene.2019.00049
doi: 10.3389/fgene.2019.00049 pubmed: 30809243 pmcid: 6379253
Tweedie S, Braschi B, Gray K et al (2021) Genenames.org: the HGNC and VGNC resources in 2021. Nucleic Acids Res 49:D939–D946. https://doi.org/10.1093/nar/gkaa980
doi: 10.1093/nar/gkaa980 pubmed: 33152070
Vassy JL, Lautenbach DM, McLaughlin HM et al (2014) The MedSeq project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials 15:85. https://doi.org/10.1186/1745-6215-15-85
doi: 10.1186/1745-6215-15-85 pubmed: 24645908 pmcid: 4113228
Vassy JL, McLaughlin HM, MacRae CA et al (2015) A one-page summary report of genome sequencing for the healthy adult. Public Health Genom 18:123–129. https://doi.org/10.1159/000370102
doi: 10.1159/000370102
Vassy JL, Davis JK, Kirby C et al (2018) How primary care providers talk to patients about genome sequencing results: risk, rationale, and recommendation. J Gen Intern Med 33:877–885. https://doi.org/10.1007/s11606-017-4295-4
doi: 10.1007/s11606-017-4295-4 pubmed: 29374360 pmcid: 5975138
Weymann D, Laskin J, Roscoe R et al (2017) The cost and cost trajectory of whole-genome analysis guiding treatment of patients with advanced cancers. Mol Genet Genom Med 5:251–260. https://doi.org/10.1002/mgg3.281
doi: 10.1002/mgg3.281
Yu Y, Bhangale TR, Fagerness J et al (2011) Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. Hum Mol Genet 20:3699–3709. https://doi.org/10.1093/hmg/ddr270
doi: 10.1093/hmg/ddr270 pubmed: 21665990 pmcid: 3159552

Auteurs

Jordan Sam (J)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

Emma Reble (E)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

Rita Kodida (R)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

Angela Shaw (A)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

Marc Clausen (M)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

Mariana Gutierrez Salazar (MG)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

Salma Shickh (S)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
University of Toronto, Toronto, ON, Canada.

Chloe Mighton (C)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
University of Toronto, Toronto, ON, Canada.

June C Carroll (JC)

University of Toronto, Toronto, ON, Canada.
Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.

Susan Randall Armel (SR)

University of Toronto, Toronto, ON, Canada.
Princess Margaret Cancer Centre, Toronto, ON, Canada.

Melyssa Aronson (M)

Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.

José-Mario Capo-Chichi (JM)

University Health Network, Toronto, ON, Canada.

Iris Cohn (I)

The Hospital for Sick Children, Toronto, ON, Canada.

Andrea Eisen (A)

Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Christine Elser (C)

University of Toronto, Toronto, ON, Canada.
Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.

Tracy Graham (T)

University of Toronto, Toronto, ON, Canada.
Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Karen Ott (K)

Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Seema Panchal (S)

Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.

Carolyn Piccinin (C)

Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.

Kasmintan A Schrader (KA)

BC Cancer, Vancouver, BC, Canada.

Raymond H Kim (RH)

University of Toronto, Toronto, ON, Canada.
Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
University Health Network, Toronto, ON, Canada.
The Hospital for Sick Children, Toronto, ON, Canada.

Jordan Lerner-Ellis (J)

University of Toronto, Toronto, ON, Canada. Jordan.Lerner-Ellis@sinaihealth.ca.
Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Jordan.Lerner-Ellis@sinaihealth.ca.
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. Jordan.Lerner-Ellis@sinaihealth.ca.
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. Jordan.Lerner-Ellis@sinaihealth.ca.

Yvonne Bombard (Y)

Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. yvonne.bombard@utoronto.ca.
University of Toronto, Toronto, ON, Canada. yvonne.bombard@utoronto.ca.
Ontario Institute for Cancer Research, Toronto, ON, Canada. yvonne.bombard@utoronto.ca.

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questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › A comprehensive genomic reporting structure...
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