Dataset Information

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

ABSTRACT:

Background

Hereditary factors contributed to breast cancer susceptibility. Low BRCA mutation prevalence was demonstrated in previous BRCA mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in.

Brca

negative breast cancers.

Methods

A total of 384 Chinese subjects with any two of high-risk factors were recruited and screened by next-generation sequencing (NGS) for 30 cancer susceptible genes. Variants with a truncating, initiation codon or splice donor/acceptor effect, or with pathogenicity demonstrated in published literature were classified into pathogenic/likely-pathogenic mutations.

Results

In total, we acquired 39 (10.2%) patients with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11, 2.9%), PTCH1 (n=7, 1.8%), RET (n=6, 1.6%) and PALB2 (n=5, 1.3%). Other mutant genes included TP53 (n=3, 0.8%), RAD51D (n=2, 0.5%), CHEK2 (n=1, 0.3%), BRIP1 (n=1, 0.3%), CDH1 (n=1, 0.3%), MRE11 (n=1, 0.3%), RAD50 (n=1, 0.3%) and PALLD (n=1, 0.3%). A splicing germline mutation, MUTYH c.934-2A>G, was a hotspot (9/384, 2.3%) in Chinese breast cancer.

Conclusions

Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Multigene testing contributes to understand genetic background of BRCA-negative breast cancer patients with high hereditary risk.

SUBMITTER: Lang GT

PROVIDER: S-EPMC7723566 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

Lang Guan-Tian GT Shi Jin-Xiu JX Huang Liang L Cao A-Yong AY Zhang Chen-Hui CH Song Chuan-Gui CG Zhuang Zhi-Gang ZG Hu Xin X Huang Wei W Shao Zhi-Ming ZM

Annals of translational medicine 20201101 21

<h4>Background</h4>Hereditary factors contributed to breast cancer susceptibility. Low <i>BRCA</i> mutation prevalence was demonstrated in previous <i>BRCA</i> mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in.<h4>Brca</h4>negative breast cancers.<h4>Methods</h4>A total of 384 Chinese subjects with any two of high-risk factors were recruited and screened by next-generation sequencing (NGS) for 30 cancer susce ...[more]

PMID: 33313162

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Project description:ObjectiveMutations or aberrant expression of genes in an organism tend not to be completely random and this cumulative effect predisposes to the development of malignant tumours. This study aims to reveal the possible aberrant expression of high frequency mutated genes, and then to investigate their role in development, prognosis, signalling pathway function and drug resistance in breast cancer.MethodsThe mutated genes in breast cancer (BRCA) clinical samples were identified and detected by high-throughput sequencing. High-frequency mutant genes were counted. Gene expression profiles and the relationship with prognosis were analysed throughout TCGA database. qRT-PCR was used to analyse the mRNA levels of the six high-frequency mutant genes in BRCA tissues and cell lines. IHC was used to analyse the protein levels of the six high-frequency mutant genes in BRCA tissues. The linear interaction, single-cell layer clustering status and the influence in immune cell infiltration degree among these six high-frequency mutant genes were analysed by bioinformatics analysis. The STITCH and cMAP datasets were used for high-frequency mutant gene interaction networks, association signalling pathway enrichment and drug-transcriptome analyses. The effects of trastuzumab on the proliferative capacity of breast cancer cells, as well as on the expression of six high-frequency mutated genes were determined by CCK8 assay.ResultsThe genes that were statistically found to have high-frequency mutations in the samples recruited in the present study by high-throughput sequencing analysis included TP53, PIK3CA, NF1, TBX3, BRCA1 and BRCA2. The expression profiles of these genes and the correlation with prognosis were further demonstrated using the TCGA database: the trend in this study was similar to that of BRCA in TCGA. The mRNA and protein expression of these genes showed that the expression of TP53, NF1, TBX3, BRCA1 and BRCA2 was higher in tumor samples than that in normal samples, with an opposite trend for PIK3CA, a similar trend was observed in BRCA cell lines. The protein expressions of TP53, NF1, TBX3, BRCA1 and BRCA2 displayed the same trend by IHC. Other correlation results include 1) the single cell layer clustering of these six genes resulted in significant clustering with few overlapping regions; 2) these six genes showed different degrees of influence on BRCA immune cell infiltration; 3) these six genes showed a significant correlation between each other; 4) the network of each gene had partially overlapping molecules; and 5) the PI3K pathway was a key association pathway in BRCA. Finally, the cell proliferation ability results confirmed the optimal concentration of trastuzumab and its effect on mRNA expression of these six genes.

Dataset Information

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

Background

Brca

Methods

Results

Conclusions

Publications

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

Similar Datasets

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