Genetic Testing

Genomic Tests by Levels of Evidence

The CDC Office of Public Health Genomics provides the following list of genomic tests and applications in practice according to three levels of evidence based on the paper by Khoury et al

. This list is provided only for informational purposes to researchers, providers, public health programs and others. The table was updated on August 23, 2012 to reflect the addition of emerging cancer genomic tests. For additional information on the updated list, read our accompanying blog.

Tier 1 genomic applications are recommended for clinical use by evidence-based panels on a systematic review of analytic validity, clinical validity and utility for specific clinical scenarios

Test/Application	Scenario	Evidence-based recommendation
Newborn screening panel of 31 core conditions	Screening all newborns at birth through public health programs	Secretary's Advisory Committee on Heritable Diseases of Newborns and Children (2011)
BRCA1/2 analysis for hereditary breast and ovarian cancer	Genetic counseling of women with specific family history patterns of breast or ovarian cancer	US Preventive Services Task Force (2005)
Lynch syndrome testing	Screening newly diagnosed cases of colorectal cancer for Lynch syndrome and cascade testing of relatives of affected Lynch syndrome cases	Evaluation of Genomic Applications in Practice and Prevention Working Group (2009) Additional Information: NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology (2011)
Familial Hypercholesterolemia	Cascade cholesterol testing with/without DNA analysis among relatives of affected persons with familial hypercholesterolemia	NICE Guideline: Identification and management of familial hypercholesterolaemia [PDF 746.30 KB] (2008)
HLA testing for abacavir sensitivity	Testing HIV patients before starting abacavir to reduce adverse effects and inform drug choice	DHHS Advisory Committee on HIV treatment [PDF 3.01 MB] (2012)
HER2 mutation testing in breast cancer	Routine testing for HER2 mutations in patients with invasive breast cancer to target therapy	NICE Guideline: Early and locally advanced breast cancer: diagnosis and treatment. [PDF 2 MB] (2009) Additional Information: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer . (2007)
EGFR mutation tumor analysis in Non-small Cell Lung Cancer	Predictive for therapy	NICE Guideline: Erlotinib for the first-line treatment of locally advanced or metastatic EGFR-TK mutation-positive non-small cell lung cancer. [PDF 189.11 KB] (2012) Additional information: NCCN Clinical Practice Guidelines in Oncology: Non–Small Cell Lung Cancer. Version 3. [PDF 1.31 MB] (2012) [by free subscription only] BCBSA Tec Evaluation - Epidermal Growth Factor Receptor Mutations and Tyrosine Kinase Inhibitor Therapy in Advanced Non-Small-Cell Lung Cancer. [PDF 195.47 KB] (2011)

Tier 2 genomic applications have demonstrated analytic and clinical validity; hold promise for clinical utility but evidence-based panels have not examined their use or found insufficient evidence for their use. Such applications may provide information for informed decision making by providers and patients

Test/Application	Scenario	Evidence-based recommendation
Breast cancer gene expression profiles	To estimate risk of recurrence of breast cancer and target therapy	Recommendations from the EGAPP Working Group: Can tumor gene expression profiling improve outcomes in patients with breast cancer? (2009) NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology. (2011)
Oncotype Dx in ER+/node negative patients	Prognostic risk recurrence and selection of treatment	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology. (2011)
ER-alpha/PgR (ESR1/PR) tumor protein analysis in Breast Cancer patients	To estimate the prognostic and predictive response to ER-alpha (ESR1)-modulating agents	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology. (2011) NCCN Task Force Report: Estrogen receptor and progesterone receptor testing in breast cancer immunohistochemistry. (2009) American Society of Clinical Oncology/College of American Pathologist guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. (2010)
Kras mutations [except c38G>A) NSCLC and CRC tumor analysis	Predictive (negative for anti-EGFR therapy); negatively prognostic in several first-line randomized studies	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011) BCBSA TEC: KRAS Mutations and Epidermal Growth Factor Receptor Inhibitor Therapy in Metastatic Colorectal Cancer. (2009, BCBSA personal communication)
CEACAM5 (CEA) serum analysis in colon cancer	Baseline monitoring/regular testing for surveillance for Colon Cancer	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011) NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 3 [PDF 1.06 MB] (2012) [by free subscription only] ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. (2006)
BRAF c.1799T>A (p.V600E) mutation tumor analysis in colon cancer	Prognostic (negative prognostic marker); Predictive (negative for anti-EGFR therapy) in colon cancer patients	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011) NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 3. [PDF 1.06 MB] (2012) [by free subscription only]
ALK gene fusion tumor analysis	Predictive for crizotinib therapy	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011) NCCN Clinical Practice Guidelines in Oncology: Non–Small Cell Lung Cancer. Version 2. (2012)
FLT3-ITD tumor analysis for Acute Myeloid Leukemia	Predictive/prognostic FLT3-ITD confers poor risk status	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011) NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. Version 2. [PDF 790.06 KB] (2011) [by free subscription only]
CEBPA mutation tumor analysis for Acute Myeloid Leukemia	Predictive/prognostic may confer better risk status	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011)
NPM1 mutation tumor analysis for Acute Myeloid Leukemia	Predictive/prognostic may confer better risk status	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011)
KIT mutation tumor analysis for Acute Myeloid Leukemia	Predictive/prognostic may confer higher risk of relapse	NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology . (2011)
Family history for common diseases	Collecting family history in primary care for risk assessment of common diseases	NIH state-of science panel found insufficient evidence (2009)
Pharmacogenomic testing	Use of pharmacogenomics tests to inform safety and effectiveness of existing medications	Pharmacogenomics information on labels of more than 80 FDA approved drugs ; The Clinical Pharmacogenetics Implementation Consortium issues guidelines to help clinicians understand how available genetic test results should be used to optimize drug therapy, rather than whether tests should be ordered.
Single gene disorders and chromosomal abnormalities	Molecular, cytogenetic biochemical and other tests available for the diagnosis, management and carrier testing for these disorders	More than 2500 genetic conditions affect millions of individuals. Diagnosis and management of these conditions may require use of genetic tests even without formal evidence synthesis and reviews by evidence panels. The NIH Genetic Testing Registry has updated information on genetic tests in practice.

Tier 3 genomic applications have not demonstrated adequate analytic validity, clinical validity, or clinical utility. This also includes applications for which evidence-based panels have recommended against their use based on the synthesis of the balance of benefits and harms. Such applications are not ready for routine practice, but may be considered in clinical and population research.

Test/Application	Scenario	Evidence-based recommendation
Genetic risk factors for common diseases	Risk assessment and disease prevention	Multiple panels have recommended against use of genetic risk factors testing. EGAPP made specific recommendations against testing for factor V Leiden and cardiogenomic profiles
Emerging genomic tests found in the CDC's GAPP Finder of the GAPP Knowledge Base	More than 400 genomic tests for various intended uses captured through horizon scanning	Almost all of these applications (except when listed above) have insufficient information on analytic or clinical validity, or clinical utility
Next Generation Sequencing/ Whole Genome Sequence	Emerging tools to help with diagnosis of rare familial diseases and provide information for assessing risk for common diseases	Rapidly evolving landscape; gaps in knowledge exist for analytic validity, clinical validity and clinical utility