AUTHOR=Li Lihong , Song Qianqian , Cao Dandan , Jiao Yuchen , Yuan Guangwen , Song Yan 

TITLE=Whole-Exome Sequencing Could Distinguish Primary Pulmonary Squamous Cell Carcinoma From Lung Metastases in Individuals With Cervical Squamous Cell Carcinoma

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 28 - 2022

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610325

DOI=10.3389/pore.2022.1610325

ISSN=1532-2807

ABSTRACT=Aims:
Metastatic cervical carcinoma is hard to be curable according to 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 remains unclear. Clinical work makes it hard to distinguish the primary pulmonary squamous cell carcinoma (PPSCC) and metastatic cervical squamous cell carcinoma (CSCC).
Methods:
Paired the primary CSCC and lung/lymph nodes metastatic lesions from 8 patients were analyzed by whole-exome sequence (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 1254 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 clonal 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, the lymph node 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. 
Conclusions:
Our data demonstrate that WES is a helpful tool in distinguishing PPSCC and metastatic CSCC.