Appendix 1 Project name: multigene detection of lung cancer | ||||||
Patient information: | ||||||
Name | XXX | Gender | Male | Pathological diagnosis | Lung adenocarcinoma | |
Hospital number | XXX | Age | X yrs | |||
Specimen information: | ||||||
Specimen number | XXX | |||||
Specimen type | Fresh tissue specimen | Tumor cell content | Frozen section assessment 80% | DNA content and quality | XXX | |
Specimen acceptance date | 2018-3-5 | Result report date | 2018-3-9 | |||
Technical brief: | Using NGS technology to detect 286 exon mutations in lung cancer (Appendices 1). Massively parallel sequencing exons and the sequence near the splicing site of these genes. Sample processing, library construction, sequencing, and analysis were all performed at the GLCI Central Laboratory. Testing platform is XXX, and analysis software is XXX. Reference genome is GRCh38. | |||||
Content of the test items: Lung cancer-related 286 gene mutations | ||||||
Test purpose and reason: Pathological diagnosis of patients with stage IV lung adenocarcinoma. Detection of gene targets provides a basis for clinical targeted therapy in patients. | ||||||
Test results: Data parameters: XX ng of nucleic acid was used to construct the sequencing library; X% of the target region was effectively sequenced to a depth of XX. Analysis results (can also be described in tabular form): 1. The status of eight actionable genes (EGFR、ALK、ROS1、RET、BRAF、HER2、KRAS、MET) in multiple international and domestic guidelines such as NCCN/IASLC/CSCO guidelines. (1) SNPs or Indels in gene sequence: EGFR, located at Chr7 (GRCh38). EGFR c.2155G>A (p.Leu858Arg), missense mutation, mutant allele frequency 19.0%; EGFR c.2369C>T (p.Thr790Met), missense mutation, mutant allele frequency 16.9%. (2) Gene copy number variation: Example: MET amplification 2.1 folds (3) Gene rearrangements or fusion: none. 2. The status of other major driver genes: Gene TP53 has a mutation of c.734G>T (p.Gly245Val) in sequence. This is a missense mutation, mutant allele frequency 15.9%. 3. Tumor Mutation Burden (TMB): The TMB value for this examination was: XX mutations/Mb. Note: Tumor mutation burden (TMB) indicates the number of somatic mutations that occur per million bases in the genome. According to existing clinical studies, TMB can be divided into three levels: TMB>=20 as TMB-High; 10<TMB<20 as TMB-Medium; TMB<=10 as TMB-Low. TMB obtained by testing plasma cfDNA could be affected by ctDNA abundance in plasma. In the case of very low ctDNA abundance (<0.5%), the ctDNA mutation burden in blood may not fully represent the mutation burden of tumor lesions. High tumor mutation burden might be in association with the efficacy of immune checkpoint inhibitors. 4. Variation of MMR and other DNA damage related genes: omitted. Note: MSI stands for microsatellite instability. Microsatellites are tandem repeats of short DNA sequences that are widely present in the genome. In the entire genome of the tumor, there are many small mutations in the microsatellites, causing some microsatellites to be unstable, which is called MSI. Due to the mismatch repair defect (dMMR), tumors can be further developed through the MSI pathway. MSI-high or MMR deficiency might be correlated with the efficacy of immune checkpoint inhibitors. 5. Variation of other potentially actionable genes: omitted. Interpretation of results: The results of this test detected EGFR c.2155G>A, p. (Leu858Arg) activation coexistence with EGFR c.2369C>T (p.Thr790Met), which may be related to the resistance of first-generation EGFR-targeted drugs, and the drug sensitivity of the third-generation drug Osimertinib (AZD 9291). TP53 mutation is very common in many cancers, which might influence the efficacy of drug treatments like EGFR TKI and others. | ||||||
Note: [1] The EGFR reference sequence is RefSeq NM_005228.3; the mutation nomenclature is written according to the HGVS nomenclature guidelines (www.hgvs.org), with the start codon A as the first nucleotide count. [2] Demonstration depth of this test: 300X. [3] Appendixes: see Appendix 1 for the list of testing gene; Appendix 2 for NGS quality parameters; Appendix 3 for list of all mutations and variations in this test. Lung cancer genetic diagnosis test background: The occurrence, development and treatment of lung cancer are closely related to gene mutations. Mutation or ectopic targeting of gene targets in lung cancer samples can benefit from targeted drug therapies, and most patients will eventually become resistant to targeted drug tyrosine kinase inhibitors (TKIs). The method can simultaneously detect multiple oncogenes, targeted drug sensitivity and resistance related genes, and provide a basis for clinical targeted therapy of lung cancer patients. In general, the major driver gene mutations in lung cancer have clinical significance in predicting the efficacy or prognosis of targeted drugs. Mutations or copy number mutations of genes such as EGFR, ALK, ROS1, RET, BRAF, HER2, and MET have a certain relationship with the corresponding targeted therapeutic efficacy. KRAS mutations may be associated with poor therapeutic efficacy of other molecular targeted therapies. Targeted drugs for EGFR mutations include Gefitinib, Erlotinib, Icotinib, Afatinib, Osimertinib, etc. EGFR T790M mutations are associated with first-generation drug-resistant and third-generation drug-sensitive effect, and EGFR C797S point mutations are associated with third-generation drug resistance. Targeted drugs forALK variation were Crizotinib, Alectinib, etc. Secondary mutations like ALK L1196M, C1156Y are associated with first-generation drug-resistance, andALK L1198F is associated with third-generation drug-resistance. Targeted drugs for ROS1 include Crizotinib, etc. Targeted drugs for RET include Cabozantinib, etc. Targeted drugs for HER2 include Transtuzumab, Afatinib, etc. Targeted drugs for MET include Crizotinib, etc. Targeted drugs for BRAF include Vemurafinib, Dabrafinib, etc. Please consult with your attending physician about treatment decision and the implications of driving gene variants in clinical specific setting. Note: The results of this analysis are only responsible for the test specimens. | ||||||
Technician (Signature): XXX Date: YYYY MM DD | ||||||
Reviewer (Signature): XXX Date: YYYY MM DD |
1: List of testing gene omitted. 2: NGS quality parameters omitted. 3: List of all mutations and variations in this test (generic descriptions of signaling pathways where major variant genes are located, other polymorphisms, or general descriptions of mutations with uncertain clinical targeting may be listed at the end of the table) omitted.