Background: The genetic heterogeneity between primary and metastatic lesions has rarely studied. Purpose: This study aims to compare the mutation profiling of key cancer-related genes in primary lung cancers and their matched lymph nodes (LN) metastasis. Methods: The gene mutation profiling of both primary cancers and their matched LN metastasis was constructed using a hybridization capture-based massively parallel sequencing assay and the sequencing of 1,408 key cancer genes in 37 NSCLC patients. Results: There are differences in the repertoire of somatic mutations and CNVs between primary lesions and metastatic lymphatic lesions in NSCLC. More mutations were discovered in the primary lesion than LN metastasis lesion, indicating that tumor mutation burden is higher in primary lesion than that in LN metastasis lesion. The copy number profiles were largely preserved through the progression of the metastasis in lung cancer individually. Regarding to the mutation context, more prevailing of signature 1 in LN metastasis lesion was observed than that of primary lesion, indicating that the spontaneous deamination of cytosine may contribute to the accumulation of mutations during tumor development and immigration. Furthermore, the LN metastasis exclusive somatic mutation (LME-SMs) genes were enriched in peptidyl-tyrosine phosphorylation, peptidyl-tyrosine modification, protein tyrosine kinase activity, and transmembrane receptor protein kinase. The KEGG pathway analysis revealed that these genes might participate in the PI3K-Akt signaling pathway, MAPK signaling pathway and Ras signaling pathway. Conclusion: Since the heterogeneity of genetic profiling exists between primary lesion and LN metastasis lesion, multi-region lesion mutation profiling is required to fully understand the progression of NSCLC, and develop an appropriate therapeutic guide. Mutations in genes involved in cell proliferation, invasion and migration may be the genetic mechanism of metastasis.
Keywords: genetic heterogeneity; metastasis; next generation sequencing; non-small cell lung cancer.