Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer

Xiao, Weikai; Zhang, Guochun; Chen, Bin; Chen, Xiaoqing; Li, Wen; Lai, Jianguo; Li, Min; Líu, Hao; Liu, Jing; Han‐Zhang, Han; Lizaso, Analyn; Liao, Ning

doi:10.3389/fonc.2021.618767

Cited by 17 publications

(14 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This difference was also observed when comparing the FUSCC Chinese TNBC cohort with publicly available data from non-Asian TNBC cohorts. This observation was consistent with a recent report by Xiao et al [ 34 ] on another Chinese breast cancer cohort, indicating that Asian patients with TNBC have a higher PIK3CA mutation rate than non-Asian patients with TNBC. A distinct characteristic of our study was the high rate of PIK3CA p.H1047R and p.H1047Q mutations in Asian patients with TNBC, which has not been reported in previous TNBC studies.…”

Section: Discussionsupporting

confidence: 93%

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

et al. 2022

View full text Add to dashboard Cite

Purpose Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC. Methods A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation. Results The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort ( p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset ( p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort ( p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets ( p = 0.002 and 0.003, respectively). Conclusion Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.

show abstract

Section: Discussionsupporting

confidence: 93%

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Detailed methods for NGS can be found in our previous research. 3 , 31 BC tissue samples were obtained through biopsy or surgery, and then processed into formalin‐fixed, paraffin‐embedded (FFPE) cell blocks. Tissue DNA was extracted from FFPE tumor blocks using QIAamp DNA FFPE tissue kit (Qiagen) and was measured using a Qubit 2.0 fluorimeter with dsDNA high sensitivity assay kit (Life Technologies).…”

Section: Methodsmentioning

confidence: 99%

“…Genomic results were obtained from NGS of breast tumors using a large 520‐gene panel. Detailed methods for NGS can be found in our previous research 3,31 . BC tissue samples were obtained through biopsy or surgery, and then processed into formalin‐fixed, paraffin‐embedded (FFPE) cell blocks.…”

Section: Methodsmentioning

confidence: 99%

Distinct clinicopathological characteristics, genomic alteration and prognosis in breast cancer with concurrent TP53 mutation and MYC amplification

Lin

Guo

et al. 2022

Thoracic Cancer

Self Cite

View full text Add to dashboard Cite

Background Both TP53 mutation and MYC amplification indicate poor outcomes in breast cancer (BC), but the clinical values of concurrent TP53 and MYC alterations have not been well‐characterized. Methods A total of 494 BC patients diagnosed at Guangdong Provincial People's Hospital (GDPH) were retrospectively analyzed. Genomic alterations were determined using next‐generation sequencing. Survival analysis was applied to assess the effects of genetic alterations on relapse‐free survival. The prognosis was verified based on 1405 patients from METABRIC cohort. Additionally, we used logistic regression to identify the factors associated with pathological complete response (pCR) after neoadjuvant chemotherapy. Results In GDPH cohort, patients with TP53/MYC co‐alteration exhibited higher grade and stage, more positive HER2 status and higher Ki67 levels, but less luminal A subtypes. They also had more mutations in genes involved in ERBB and TGF‐β signaling pathways, as well as exclusive FANCG/CDKN2B/QKI copy number amplifications and SUFU/HIST3H3/ERCC4/JUN/BCR mutations. Concurrent TP53 and MYC alterations independently increased hazards of relapse (HR, 5.425; 95% CI: 2.019–14.579; p < 0.001). They maintained independent significance for relapse‐free (HR, 1.310; 95% CI: 1.012–1.697; p = 0.041) and overall survival (HR, 1.373; 95% CI: 1.093–1.725; p = 0.006) in METABRIC cohort. Among the 81 patients receiving chemotherapy, TP53 mutation (OR, 5.750; 95% CI: 1.553–25.776; p = 0.013) and earlier stage (OR, 0.275; 95% CI 0.088–0.788; p = 0.020) were associated with pCR, while the co‐alteration did not serve as an independent predictor ( p = 0.199). Conclusions TP53/MYC co‐alteration was associated with distinct clinicopathological and genomic features. They also conferred unfavorable prognosis in BC patients, and did not improve pCR after neoadjuvant chemotherapy.

show abstract

“…Alterations in copy numbers are often observed at pre-malignant stages because 15 to 44% of atypical ductal hyperplasia are aneuploid [ 122 ]. The frequently mutated and/or amplified genes related to BC include phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), transcription factor tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), proto-oncogene myelocytomatosis (MYC), cyclin D1 (CCND1), human epidermal growth factor receptor 2/proto-oncogene C-ErbB-2/Erb-B2 receptor tyrosine kinase 2 (ERBB2), fibroblast growth factor receptor 1 (FGFR1), and transcription factor GATA binding protein 3 (GATA3) [ 25 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ]. To address the heterogeneity, classification systems have evolved to improve treatment choices and prognosis [ 134 ].…”

Section: Pathology Risk Factors and Treatmentmentioning

confidence: 99%

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer

Silva

Alcorn

2022

Cancers

View full text Add to dashboard Cite

Cancer is a global issue, and it is expected to have a major impact on our continuing global health crisis. As populations age, we see an increased incidence in cancer rates, but considerable variation is observed in survival rates across different geographical regions and cancer types. Both breast and prostate cancer are leading causes of morbidity and mortality worldwide. Although cancer statistics indicate improvements in some areas of breast and prostate cancer prevention, diagnosis, and treatment, such statistics clearly convey the need for improvements in our understanding of the disease, risk factors, and interventions to improve life span and quality of life for all patients, and hopefully to effect a cure for people living in developed and developing countries. This concise review compiles the current information on statistics, pathophysiology, risk factors, and treatments associated with breast and prostate cancer.

show abstract

Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer

Cited by 17 publications

References 40 publications

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

Distinct clinicopathological characteristics, genomic alteration and prognosis in breast cancer with concurrent TP53 mutation and MYC amplification

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer

Contact Info

Product

Resources

About