AUTHOR=Hao Chunfang , Wang Chen , Lu Ning , Zhao Weipeng , Li Shufen , Zhang Li , Meng Wenjing , Wang Shuling , Tong Zhongsheng , Zeng Yanwu , Lu Leilei 

TITLE=Gene Mutations Associated With Clinical Characteristics in the Tumors of Patients With Breast Cancer

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.778511

DOI=10.3389/fonc.2022.778511

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Clinical characteristics including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) are important biomarkers in the treatment of breast cancer, but how genomic mutations affect their status is rarely studied. This study aimed at finding genomic mutations associated with these clinical characteristics.</p></sec><sec><title>Methods</title><p>There were 160 patients with breast cancer enrolled in this study. Samples from those patients were used for next-generation sequencing, targeting a panel of 624 pan-cancer genes. Short nucleotide mutations, copy number variations, and gene fusions were identified for each sample. Fisher’s exact test compared each pair of genes. A similarity score was constructed with the resulting <italic>P</italic>-values. Genes were clustered with the similarity scores. The identified gene clusters were compared to the status of clinical characteristics including ER, PR, HER2, and a family history of cancer (FH) in terms of the mutations in patients.</p></sec><sec><title>Results</title><p>Gene-by-gene analysis found that <italic>CCND1</italic> mutations were positively correlated with ER status while <italic>ERBB2</italic> and <italic>CDK12</italic> mutations were positively correlated with HER2 status. Mutation-based clustering identified four gene clusters. Gene cluster 1 (<italic>ADGRA2</italic>, <italic>ZNF703</italic>, <italic>FGFR1</italic>, <italic>KAT6A</italic>, and <italic>POLB</italic>) was significantly associated with PR status; gene cluster 2 (<italic>COL1A1</italic>, <italic>AXIN2</italic>, <italic>ZNF217</italic>, <italic>GNAS</italic>, and <italic>BRIP1</italic>) and gene cluster 3 (<italic>FGF3</italic>, <italic>FGF4</italic>, <italic>FGF19</italic>, and <italic>CCND1</italic>) were significantly associated with ER status; gene cluster 2 was also negatively associated with a family history of cancer; and gene cluster 4 was significantly negatively associated with age. Patients were classified into four corresponding groups. Patient groups 1, 2, 3, and 4 had 24.1%, 36.5%, 38.7%, and 41.3% of patients with an FDA-recognized biomarker predictive of response to an FDA-approved drug, respectively.</p></sec><sec><title>Conclusion</title><p>This study identified genomic mutations positively associated with ER and PR status. These findings not only revealed candidate genes in ER and PR status maintenance but also provided potential treatment targets for patients with endocrine therapy resistance.</p></sec>