Multi-Gene Panel NGS Examples
Multi-gene NGS panels are pre-defined sets of genes sequenced simultaneously to identify pathogenic variants relevant to specific clinical contexts, with examples including breast cancer panels (7-37 genes like BRCA1/2, PALB2, ATM, CHEK2), myeloid neoplasm panels (22-48 genes including JAK2, CALR, MPL), and pharmacogenomics panels (9+ genes for drug metabolism). 1, 2, 3, 4
Cancer Germline Testing Panels
Breast Cancer Multi-Gene Panels
The most clinically established example involves breast cancer susceptibility genes (BCSGs), where panels vary widely from 7 to 37 genes depending on the provider and country 2. These typically include:
- High-penetrance genes: BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, PALB2
- Moderate-penetrance genes: ATM, CHEK2, BARD1, RAD51C, RAD51D
- "HBOPP genes" (hereditary breast-ovarian-prostate-pancreatic): BRCA1/2, PALB2, ATM, CHEK2, RAD51C, RAD51D, BARD1 2
The ASCO 2024 guideline emphasizes that panel selection should be informed by personal and family cancer history, with genes included based on clinical validity (established association with cancer) 1. Smaller, focused panels avoid genes with uncertain clinical validity and reduce variants of uncertain significance (VUS), which can lead to misinterpretation and overtreatment 1.
Pan-Cancer Panels
Some patients may be offered pan-cancer panels (typically >50 genes) to address multiple testing requirements simultaneously, particularly when family history suggests multiple cancer syndrome possibilities 2.
Hematologic Malignancy Panels
Myeloproliferative Neoplasm Panels
A validated 22-gene NGS panel for myeloproliferative neoplasms (MPNs) including essential thrombocythemia, polycythemia vera, and primary myelofibrosis has been developed, targeting driver mutations and associated genes 3.
For broader myeloid neoplasms (AML, MDS, MPN), a 48-gene panel has demonstrated 99.6% sensitivity and 100% specificity, specifically designed to capture technically challenging genes like CEBPA, CALR, and FLT3-ITD 5. This panel detected clinically significant mutations in 77% of AML patients, 48% of MDS patients, and 45% of MPN patients 5.
Pharmacogenomics Panels
The Ion AmpliSeq Pharmacogenomics Panel covering 9 genes has been validated for routine clinical use, achieving >96.77% accuracy, 100% sensitivity, and >95.31% specificity for identifying genetic variations that influence drug response 4. This represents a practical application for personalizing medication selection and dosing.
Solid Tumor Panels
A 61-gene oncopanel targeting cancer-associated genes achieved 98.23% sensitivity and 99.99% specificity, detecting actionable mutations in KRAS, EGFR, ERBB2, PIK3CA, TP53, and BRCA1 with a 4-day turnaround time 6.
Key Clinical Considerations
The technological economy of NGS means testing 200 genes costs little more than 2-20 genes, but this doesn't justify indiscriminate panel expansion 2. Larger panels increase VUS detection rates, which can cause patient anxiety and inappropriate clinical interventions 1.
Panel selection should prioritize genes with established clinical validity and actionable management implications - meaning genes where identification of a pathogenic variant changes surveillance, prevention, or treatment strategies 1, 2. The detection limit for most validated clinical panels is approximately 1-5% variant allele frequency 3, 5.