Abstract
Aims: Metastatic cervical carcinoma is hard to cure using traditional treatment and new therapeutic approaches are needed. However, the process of clonal evolution and the molecular alterations that contribute to tumor progression from primary to metastatic carcinoma remain unclear. It is currently difficult to distinguish between the primary pulmonary squamous cell carcinoma (PPSCC) and metastatic cervical squamous cell carcinoma (CSCC). Methods: Paired primary CSCC and lung/lymph nodes metastatic lesions from eight patients were analyzed by whole-exome sequencing (WES). WES data of matched specimens and normal samples were aligned to the human reference genome and analyzed to identify somatic mutations in primary and metastatic lesions. Results: A total of 1,254 somatic variants were identified. All the primary lesions and metastatic lesions shared mutations, the percentage of shared mutations between primary lesions and corresponding metastatic lesions varied significantly, ranging from 6% to 70%. In other words, all the metastatic lesions are clonally related to primary lesions, confirming WES could prove they are metastatic from the cervix but not PPSCC. We tried to apply a gene panel to help distinguish PPSCC and metastatic CSCC but failed because the mutations were widely distributed in CSCC. Interestingly, lymph nodes metastasis (LNM) harbored fewer cancer driver mutations than primary CSCC specimens with a significant difference. Besides this, there was no significant difference in somatic mutations and copy number variation (CNV) between primary and metastatic CSCC. Conclusion: Our data demonstrate that WES is an additional helpful tool in distinguishing PPSCC and metastatic CSCC, especially for certain difficult cases.