AUTHOR=Chen Bo , Guo Liping , Li Kai , Xiao Weikai , Li Yingzi , Li Cheukfai , Mok Hsiaopei , Cao Li , Lin Jiali , Wei Guangnan , Zhang Guochun , Liao Ning 

TITLE=Association of Body Mass Index With Somatic Mutations in Breast Cancer

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.613933

DOI=10.3389/fonc.2021.613933

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>The relationship between body mass index (BMI) and the prognosis or treatment response in patients with breast cancer has been demonstrated in previous studies, but the somatic mutation profiles in breast cancer patients with different BMIs have not been explored.</p></sec><sec><title>Methods</title><p>In the present study, the somatic mutation profiles in 421 female breast cancer patients who were stratified into three subgroups based on BMI (normal weight, overweight/obese, and underweight) were investigated. Capture-based targeted sequencing was performed using a panel comprising 520 cancer-related genes.</p></sec><sec><title>Results</title><p>A total of 3547 mutations were detected in 390 genes. In breast cancer patients with different BMI statuses, the tumors exhibited high mutation frequency and burden. <italic>TP53</italic> was the most common gene in the three groups, followed by <italic>PIK3CA</italic>, <italic>ERBB2</italic>, and <italic>CDK12.</italic> Meanwhile, the mutation hotspots in <italic>TP53</italic> and <italic>PIK3CA</italic> were the same in the three BMI groups. More <italic>JAK1</italic> mutations were identified in underweight patients than those in normal patients. Except for <italic>JAK1</italic>, differentially mutated genes in postmenopausal patients were completely different from those in premenopausal patients. The distribution of mutation types was significantly different among BMI groups in the postmenopausal group. Underweight patients in the postmenopausal group harbored more <italic>TP53</italic> mutations, more amplifications, and more mutations in genes involved in the WNT signaling pathway.</p></sec><sec><title>Conclusions</title><p>Our next-generation sequencing (NGS)-based gene panel analysis revealed the gene expression profiles of breast cancer patients with different BMI statuses. Although genes with high mutation frequency and burden were found in different BMI groups, some subtle differences could not be ignored. <italic>JAK1</italic> mutations might play a vital role in the progression of breast cancer in underweight patients, and this needs further analysis. Postmenopausal underweight patients with breast cancer have more aggressive characteristics, such as <italic>TP53</italic> mutations, more amplifications, and more mutations in genes involved in the WNT signaling pathway. This study provides new evidence for understanding the characteristics of breast cancer patients with different BMIs.</p></sec>