Molecular testing of non-small cell lung cancer (NSCLC) is currently the standard of care for guiding the use FDA-approved targeted therapies such as inhibitors of EGFR, ALK and ROS1. In addition, there is growing clinical evidence supporting the efficacy of other treatments such as BRAF and MEK inhibitors for BRAF V600E-mutated NSCLC, crizotinib for NSCLC with MET exon 14 skipping mutations or high level MET amplification, various tyrosine kinase inhibitors (TKI) for NSCLC with RET rearrangements and ERBB2 antibodies and TKI for NSCLC with ERBB2 mutations. The use FDA-approved drugs for an off-label indication, such as these, and enrollment in clinical trials based on molecular findings is an important aspect of the care of patients with advanced stage NSCLC. This assay is designed to provide comprehensive molecular results relevant for both standard of care and emerging/investigational clinical actions. This DNA and RNA based, next-generation sequencing test targets 50 genes to detect substitution and insertion/deletion mutations (35 genes), gene amplifications (19 genes), and gene fusions (21 genes). Detectable variants relevant for NSCLC include, but are not limited to, mutations of EGFR, KRAS, NRAS, BRAF, ERBB2, MET (including exon 14 skipping), MAP2K1, PIK3CA, AKT1, FGFR2, FGFR3, DDR2, ALK, ROS1 and RET; amplification of EGFR, FGFR1, ERBB2, KRAS, PIK3CA, and MYC; and rearrangements of ALK, ROS1, RET, NTRK1/2/3, BRAF, and FGFR3. A complete list of sequenced regions, genes assessed for amplification and detectable fusion transcripts is available below.
This test will only detect the mutations within specific gene regions, relatively high-level copy number gains involving specific genes and specific gene fusions (See Additional Information below for specific information). This test may fail to detect low-level copy number gains within evaluated genes (<8) or molecular alterations below the limit of detection of this assay (approximately 5%). Discordant results are rarely observed between metastatic and primary tumors. This test cannot distinguish between somatic and germline alterations. Additional testing may be required if there is concern for a clinically relevant germline alteration. The clinical implications of the findings as indicated in the test report may change based on evolution of the scientific literature.
- PIK3CA exons 2, 5, 7, 8, 10, 14, 19 and 21
- AKT1 exons 4 and 7
- ERBB2 (HER2) exons 19-21
- BRAF exons 11 and 15
- NRAS exons 2-4
- KRAS exons 2-4
- EGFR exons 3, 7, 15 and 18-21
- NSCLC Mutation Panel by NGS
- Oncomine genomic profiling
- Oncomine genomic profiling
For formalin-fixed, paraffin-embedded tissue, a block containing an area with a high percentage of neoplastic cells (for micro-/macro-dissection) is preferred. Unstained, UNBAKED slides (5-8, 10-micron slides; 10-15 if few neoplastic cells are present) with associated H&E stained slide are also acceptable. Decalcified tissue or other fixatives will be accepted and the assay attempted, however these may result in failed testing due to degraded nucleic acid. Both blocks and slides should be stored at room temperature. A Diff-Quik or Papanicolaou stained aspirate smear (preferable containing a high percentage and overall amount of neoplastic cells) is also acceptable. Store at room temperature.