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Published in:

01-10-2016 | Original Article

Evaluation of laboratory perspectives on hereditary cancer panels

Authors: Jessica Stoll, Scott M. Weissman, Nicole Hook, Christina Selkirk, Amy Knight Johnson, Anna Newlin, Kristen J. Vogel Postula

Published in: Familial Cancer | Issue 4/2016

Abstract

Genetic counseling and testing for hereditary cancer susceptibility is a rapidly evolving field and partly a result of next-generation sequencing (NGS) allowing analysis of multiple cancer susceptibility genes simultaneously. This qualitative study explored laboratory perspectives on hereditary cancer panels. Semi-structured interviews were conducted with representatives of clinical laboratories offering hereditary cancer panels via NGS. Several themes emerged from the responses pertaining to hereditary cancer panel development, the importance of communication of panel properties with patients, variant reporting policies, and the future of hereditary cancer gene testing. Clinical utility was discussed as primary consideration during panel development. In addition, while participants indicated gene and syndrome overlap prompted panel development in general, laboratories differed in their opinions of whether phenotypic overlap warrants offering pan-cancer panels only versus cancer specific panels. Participants stressed the importance of patients understanding implications of panel testing, including what is tested for and limitations of testing. While all laboratories discussed the limitations of a variant of uncertain significance result, they differed significantly in their reporting methods. This study provides healthcare providers information on the laboratory approach to panel testing, highlighting both commonalities and differences in laboratory approaches, and may allow providers to make more informed decisions when ordering hereditary cancer panels.

Riley BD, Culver JO, Skrzynia C et al (2012) Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns 21(2):151–161CrossRefPubMed

Niendorf K, Thomas B (2013) Genetic counseling for cancer: technology promises better screening for hereditary cancer patients. Curr Genet Med Rep 1:135–141CrossRef

Stoffel EM, Kastrinos F (2014) Familial colorectal cancer, beyond Lynch syndrome. Clin Gastroenterol Hepatol 12(7):1059–1068CrossRefPubMed

Giardello FM, Allen JI, Axilbund JE et al (2014) Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer. Gastroenterology 147(2):502–526CrossRef

NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal Version 2.2014 (2014) http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 6 March 2015

Weissman SM, Burt R, Church J et al (2012) Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline. J Genet Couns 21(4):484–493CrossRefPubMed

Morak M, Heidenreich B, Keller G et al (2014) Biallelic MUTYH mutations can mimic Lynch syndrome. Eur J Hum Genet 22(11):1334–1337CrossRefPubMedPubMedCentral

LaDuca H, Stuenkel AJ, Dolinsky JS et al (2014) Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med 16(11):830–837CrossRefPubMedPubMedCentral

Pritchard CC, Smith C, Salipante SJ et al (2012) ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 14(4):357–366CrossRefPubMedPubMedCentral

10.

Domchek SM, Bradbury A, Garber JE, Offit K, Robson ME (2013) Multiplex genetic testing for cancer susceptibility: out on the high wire without a net? J Clin Oncol 31(10):1267–1270CrossRefPubMed

11.

Tung N, Battelli C, Allen B et al (2012) Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer 121(1):25–33CrossRef

12.

Hiraki S, Rinella ES, Schnabel F, Oratz R, Ostrer H (2014) Cancer risk assessment using genetic panel testing: considerations for clinical application. J Genet Couns 23(4):604–617CrossRefPubMed

13.

Bonadona V, Bonaiti B, Olschwang S et al (2011) Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 305(22):2304–2310CrossRefPubMed

14.

Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333CrossRefPubMedPubMedCentral

15.

Daly MB, Pilarski R, Axilbund JE et al (2014) Genetic/familial high-risk assessment: breast and ovarian, version 2.2014. J Natl Compr Canc Netw 12(9):1326–1338PubMed

16.

Mauer CB, Pirzadeh-Miller SM, Robinson LD, Euhus DM (2013) The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience. Genet Med 16(5):407–412CrossRefPubMed

17.

Kurian AW, Hare EE, Mills MA et al (2014) Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. J Clin Oncol 32(19):2001–2009CrossRefPubMedPubMedCentral

18.

Miller-Samuel S, Macdonald DJ, Weitzel JN et al (2011) Variants of uncertain significance in breast cancer-related genes: real world implications for a clinical conundrum. Part one: clinical genetics recommendations. Semin Oncol 38(4):469–480CrossRefPubMed

19.

Fecteau H, Vogel KJ, Hanson K, Morril-Cornelius S (2014) The evolution of cancer risk assessment in the era of next-generation sequencing. J Genet Couns 23(4):633–639CrossRefPubMed

20.

Selkirk CG, Vogel KJ, Newlin AC et al (2014) Cancer genetic testing panels for inherited cancer susceptibility: the clinical experience of a large adult genetics practice. Fam Cancer 13(4):527–536CrossRefPubMed

21.

Easton DF, Pharoah PDP, Antoniou AC et al (2015) Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med 372(23):2243–2257CrossRefPubMedPubMedCentral

22.

Thomas DR (2006) A general inductive approach for analyzing qualitative evaluation data. Am J Eval 27(2):237–246CrossRef

23.

Walsh T, Lee MK, Casadei S et al (2011) Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci USA 107(28):12629–12633CrossRef

24.

Pennington KP, Swisher EM (2011) Hereditary ovarian cancer: beyond the usual suspects. Gynecol Oncol 124(2):347–353CrossRef

25.

Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K, American Society of Clinical Oncology (2010) American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 28(5):893–901CrossRefPubMed

26.

Walsh T, Casadei S, Lee MK et al (2011) Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci USA 108(44):18032–18037CrossRefPubMedPubMedCentral

27.

Stadler ZK, Schrader KA, Vijai J, Robson ME, Offit K (2014) Cancer genomics and inherited risk. J Clin Oncol 32(7):687–698CrossRefPubMed

28.

Mester JL, Moore RA, Eng C (2013) PTEN germline mutations in patients initially tested for other hereditary cancer syndromes: would use of risk assessment tools reduce genetic testing? Oncologist 18(10):1083–1090CrossRefPubMedPubMedCentral

29.

Radford C, Prince A, Lewis K, Pal T (2014) Factors which impact the delivery of genetic risk assessment services focused on inherited cancer genomics: expanding the role and reach of certified genetics professionals. J Genet Couns 23(4):522–530CrossRefPubMed

30.

Fitzgerald RC, Hardwick R, Huntsman D et al (2003) Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 47(7):436–444CrossRef

31.

Bruinooge SS (2003) American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol 21(12):2397–2406CrossRef

32.

Pyeritz RE (2011) The coming explosion in genetic testing: Is there a duty to recontact? N Engl J Med 365(15):1367–1369CrossRefPubMed

33.

O’Neill SC, Rini C, Goldsmith RE, Valdimarsdottir H, Cohen LH, Schwartz MD (2009) Distress among women receiving uninformative BRCA1/2 results: 12-month outcomes. Psychooncology 18(10):1088–1096CrossRefPubMedPubMedCentral

34.

Petrucelli N, Lazebnik N, Huelsman KM, Lazebnik RS (2002) Clinical interpretation and recommendations for patients with a variant of uncertain significance in BRCA1 or BRCA2: a survey of genetic counseling practice. Genet Test 6(2):107–113CrossRefPubMed

35.

Vos J, Otten W, van Asperen C, Jansen A, Menko F, Tibben A (2008) The counsellees’ view of an unclassified variant in BRCA1/2: recall, interpretation and impact on life. Psychooncology 17(8):822–830CrossRefPubMed

36.

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(5):405–424CrossRefPubMedPubMedCentral

37.

Nelen M, Veltman JA (2012) Genome and exome sequencing in the clinic: unbiased genomic approaches with a high diagnostic yield. Pharmacogenomics 13(5):511–514CrossRefPubMed

38.

Klee EW, Hoppman-Chaney NL, Ferber MJ (2011) Expanding DNA diagnostic panel testing: Is more better? Expert Rev Mol Diagn 11(7):703–709CrossRefPubMed

39.

Faruki H (2013) Genomic testing: the clinical laboratory perspective. Clin Pharmacol Ther 94(2):190–192CrossRefPubMed

Title: Evaluation of laboratory perspectives on hereditary cancer panels
Authors: Jessica Stoll
Scott M. Weissman
Nicole Hook
Christina Selkirk
Amy Knight Johnson
Anna Newlin
Kristen J. Vogel Postula
Publication date: 01-10-2016
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 4/2016
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-016-9880-x

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