Next-generation sequencing (NGS) technologies have ushered in a new era of genetic testing with the capability of sequencing multiple genes at a single time.1,2 The overall approach of NGS involves shearing and immobilizing DNA template molecules, usually on a solid surface, for simultaneous sequencing reactions (typically millions to billions) to be performed in parallel.3,4 Gene panel testing refers to sequencing multiple prespecified genes using NGS sequencing platforms. Testing can be performed in the context of assessing for mutations in the germline related to inherited cancer risk, or testing for genetic mutations in a solid tumor or leukemia/lymphoma to gain insights into somatic mutations involved in carcinogenesis and potentially inform targets for treatment.2 Recently, gene panel tests (or multigene panels) using NGS technology have been introduced by several commercial genetic testing laboratories and academic institutions. This article provides an overview of gene panel testing for inherited cancer risk assessment and highlights the potential benefits and emerging challenges of this novel approach to genetic testing.
Ms. Forman has disclosed that she is on the Genetic Counseling Advisory Board for Myriad Genetics, Inc. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
National Cancer Institute. Cancer Genetics Overview (PDQ). Available at: http://www.cancer.gov/cancertopics/pdq/genetics/overview/healthprofessional/allpages#5. Accessed May 4 2014.
EastonDFDeffenbaughAMPrussD. A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet2007;81:873–883.
ThompsonBAGoldgarDEPatersonC. A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry. Hum Mutat2013;34:200–209.
DomchekSMBradburyAGarberJE. Multiplex genetic testing for cancer susceptibility: out on the high wire without a net?J Clin Oncol2013;31:1267–1270.
WalshTCasadeiSLeeMK. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A2011;108:18032–18037.
ChurpekJWalshTZhengY. Inherited mutations in breast cancer genes in African American breast cancer patients revealed by targeted genomic capture and next-generation sequencing [abstract]. J Clin Oncol2013;31(Suppl):Abstract CRA1501.
YurgelunMAllenBKaldateR. Germline mutations identified by a 25-gene panel in patients undergoing Lynch syndrome testing. Presented at the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC) Annual Meeting; October 7-8, 2013; Anaheim, California.
NorquistBMPenningtonKPAgnewKJ. Characteristics of women with ovarian carcinoma who have BRCA1 and BRCA2 mutations not identified by clinical testing. Gynecol Oncol2013;128:483–487.
McWilliamsRRPetersenGMRabeKG. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma. Cancer2010;116:203–209.
RebbeckTRMitraNDomchekSM. Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers. Cancer Res2009;69:5801–5810.
DomchekSMFriebelTMSingerCF. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA2010;304:967–975.
GroverSStoffelEMMercadoRC. Colorectal cancer risk perception on the basis of genetic test results in individuals at risk for Lynch syndrome. J Clin Oncol2009;27:3981–3986.
CulverJOBrinkerhoffCDClagueJ. Variants of uncertain significance in BRCA testing: evaluation of surgical decisions, risk perception, and cancer distress. Clin Genet2013;84:464–472.
HirakiSRinellaESSchnabelF. Cancer risk assessment using genetic panel testing: considerations for clinical application. J Genet Couns2014;23:604–617.
HallMJReidJEBurbidgeLA. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breastovarian cancer. Cancer2009;115:2222–2233.
FacioFMLeeKO’DanielJM. A genetic counselor’s guide to using next-generation sequencing in clinical practice. J Genet Couns2014;23:455–462.
FrostCJVenneVCunninghamDGerritsen-McKaneR. Decision making with uncertain information: learning from women in a high risk breast cancer clinic. J Genet Couns2004;13:221–236.
FitzgeraldRCHardwickRHuntsmanD. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet2010;47:436–444.