KEY FACTS
TERMINOLOGY
Definitions
- Germline mutation: Identified in inherited genetic material in normal cells, used for germline genetic testing (typically sourced from blood or saliva)
- Somatic/tumor mutation: Found only in tumor DNA, not inherited
- Penetrance: Proportion of individuals with given pathogenic gene mutation that show diseased phenotype
- Pathogenic/likely pathogenic mutation: Variant in DNA that is known to be disease causing; positive genetic test
- Variant of unknown significance (VUS)
- Found in DNA, may or may not be disease causing
- Generally, no clinical action is taken for VUS
- Over time, some are reclassified as pathogenic, but most are benign
- Personal/family history of ovarian cancer
- Fallopian tube and primary peritoneal cancer
- Invasive epithelial ovarian cancers
- i.e., exclude germ cell ovarian cancers
- Personal/family history of aggressive/metastatic prostate cancer: Includes Gleason 7 or higher tumors &/or proven metastatic prostate cancer (not based on PSA levels alone)
- Personal/family history of pancreatic cancer: Includes adenocarcinoma; excludes endocrine tumors of pancreas
- Single nucleotide polymorphism (SNP): Small variation in DNA sequence; most are common, but some are rare; may or may not impact disease risk
CLINICAL IMPLICATIONS
High Risk of Breast Cancer
Rare Cancer Syndromes
Considerations in Genetic Testing
Selected References
- NCCN: Genetics Screening. https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed April 6, 2019
- Beitsch PD et al: Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle? J Clin Oncol. 37(6):453-460, 2019
- Corso G et al: Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect. J Med Genet. 55(7):431-41, 2018
- Schon K et al: Clinical implications of germline mutations in breast cancer: TP53. Breast Cancer Res Treat. 167(2):417-23, 2018
- Afghahi A et al: The changing landscape of genetic testing for inherited breast cancer predisposition. Curr Treat Options Oncol. 18(5):27, 2017
- Couch FJ et al: Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 3(9):1190-6, 2017
- Daly MB et al: NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017. J Natl Compr Canc Netw. 15(1):9-20, 2017
- Howell SJ et al: Increased risk of breast cancer in neurofibromatosis type 1: current insights. Breast Cancer (Dove Med Press). 9:531-6, 2017
- Lieberman S et al: Population screening for BRCA1/BRCA2 mutations: lessons from qualitative analysis of the screening experience. Genet Med. 19(6):628-34, 2017
- Slavin TP et al: The contribution of pathogenic variants in breast cancer susceptibility genes to familial breast cancer risk. NPJ Breast Cancer. 3:22, 2017
- Kurian AW et al: Refining breast cancer risk stratification: additional genes, additional information. Am Soc Clin Oncol Educ Book. 35:44-56, 2016
- Mai PL et al: Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer. 122(23):3673-81, 2016
- Antoniou AC et al: Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 371(6):497-506, 2014
- Robson ME et al: American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 28(5):893-901, 2010
- Eng C et al: PTEN Hamartoma Tumor Syndrome, updated June 12, 2016, in Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews®[Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018
- McGarrity TJ et al: Peutz-Jeghers Syndrome in Gene Reviews, Adam MP, Ardinger HH, Pagon RA, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2018.
- Petrucelli N et al: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer in Gene Reviews, Adam MP, Ardinger HH, Pagon RA, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2018.
- Genetic Information Non-discrimination Act
- Kaurah P et al: Hereditary Diffuse Gastric Cancer in Gene Reviews, Adam MP, Ardinger HH, Pagon RA, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2018.
Related Differential Diagnoses
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