AUTHOR=Jiang Cen , Lu Yiyi , Liu Hua , Cai Gang , Peng Zhao , Feng Weiwei , Lin Lin 

TITLE=Clinical characterization and genomic landscape of gynecological cancers among patients attending a Chinese hospital

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1143876

DOI=10.3389/fonc.2023.1143876

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Gynecological cancers are the most lethal malignancies among females, most of which are associated with gene mutations. Few studies have compared the differences in the genomic landscape among various types of gynecological cancers. In this study, we evaluated the diversity of mutations in different gynecological cancers.</p></sec><sec><title>Methods</title><p>A total of 184 patients with gynecological cancer, including ovarian, cervical, fallopian tube, and endometrial cancer, were included. Next-generation sequencing was performed to detect the mutations and tumor mutational burden (TMB). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were also conducted.</p></sec><sec><title>Results</title><p>We found that 94.57% of patients had at least one mutation, among which single nucleotide variants, insertions and InDels were in the majority. <italic>TP53, PIK3CA, PTEN, KRAS, BRCA1, BRCA2, ARID1A, KMT2C, FGFR2</italic>, and <italic>FGFR3</italic> were the top 10 most frequently mutated genes. Patients with ovarian cancer tended to have higher frequencies of <italic>BRCA1</italic> and <italic>BRCA2</italic> mutations, and the frequency of germline <italic>BRCA1</italic> mutations (18/24, 75.00%) was higher than that of <italic>BRCA2</italic> (11/19, 57.89%). A new mutation hotspot in <italic>BRCA2</italic> (I770) was firstly discovered among Chinese patients with gynecological cancer. Patients with <italic>TP53</italic>, <italic>PIK3CA</italic>, <italic>PTEN</italic>, and <italic>FGFR3</italic> mutations had significantly higher TMB values than those with wild-type genes. A significant cross was discovered between the enriched KEGG pathways of gynecological and breast cancers. GO enrichment revealed that the mutated genes were crucial for the cell cycle, neuronal apoptosis, and DNA repair.</p></sec><sec><title>Conclusion</title><p>Various gynecological cancer types share similarities and differences both in clinical characterization and genomic mutations. Taken together with the results of TMB and enriched pathways, this study provided useful information on the molecular mechanism underlying gynecological cancers and the development of targeted drugs and precision medicine.</p></sec>