Candidate gene analysis of BRCA1/2 mutation-negative high-risk Russian breast cancer patients

Sokolenko, Anna P.; Preobrazhenskaya, Elena V.; Aleksakhina, Svetlana N.; Iyevleva, Aglaya G.; Mitiushkina, Natalia V.; Zaitseva, Olga A.; Yatsuk, Olga S.; Tiurin, Vladislav I.; Strelkova, Tatiana N.; Togo, Alexandr V.; Imyanitov, Evgeny N.

doi:10.1016/j.canlet.2015.01.022

Cited by 33 publications

(26 citation statements)

References 24 publications

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“…Accumulating evidence demonstrates that inactivation of the BRD7 gene contributes to the development of many human cancers by transcriptional dysregulation [1,2,[6][7][8][9][10][11][12][13]. BRD7 regulates signaling pathways that involve cell growth, apoptosis, cell cycle, and mobility [14][15][16][17][18][19][20][21].…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence indicates that BRD7 was also down-regulated in multiple types of human cancer, including breast [6], prostate [7], endometrial [8], colorectal [9], ovarian [10], and pancreas cancer [11], glioma [12], and osteosarcoma [13]. BRD7 can inhibit cell growth through multiple mechanisms, including cell cycle arrest and apoptosis [14,15].…”

Section: Introductionmentioning

confidence: 98%

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Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network

Xiong

Zhou

et al. 2015

Mol Cell Biochem

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BRD7 is a single bromodomain-containing protein that functions as a subunit of the SWI/SNF chromatin-remodeling complex to regulate transcription. It also interacts with the well-known tumor suppressor protein p53 to trans-activate genes involved in cell cycle arrest. In this paper, we report an integrative analysis of genome-wide chromatin occupancy of BRD7 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and digital gene expression (DGE) profiling by RNA-sequencing upon the overexpression of BRD7 in human cells. We localized 156 BRD7-binding peaks representing 184 genes by ChIP-sequencing, and most of these peaks were co-localized with histone modification sites. Four novel motifs were significantly represented in these BRD7-enriched regions. Ingenuity pathway analysis revealed that 22 of these BRD7 target genes were involved in a network regulating cell death and survival. DGE profiling identified 560 up-regulated genes and 1088 down-regulated genes regulated by BRD7. Using Gene Ontology and pathway analysis, we found significant enrichment of the cell cycle and apoptosis pathway genes. For the integrative analysis of the ChIP-seq and DEG data, we constructed a regulating network of BRD7 downstream genes, and this network suggests multiple feedback regulations of the pathways. Furthermore, we validated BIRC2, BIRC3, TXN2, and NOTCH1 genes as direct, functional BRD7 targets, which were involved in the cell cycle and apoptosis pathways. These results provide a genome-wide view of chromatin occupancy and the gene regulation network of the BRD7 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network

Xiong

Zhou

et al. 2015

Mol Cell Biochem

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“…Thus far, multigene panel testing of BC predisposition genes have been extensively conducted in African Americans, Caucasian, Ashkenazi Jewish and Slavs, while the data is relatively rare in other populations. China is the most populous country in the world, and analysis of Chinese BC patients may reveal new disease‐causing genes and novel pathogenic mutations.…”

Section: Introductionmentioning

confidence: 99%

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer

Jing

Wei

et al. 2018

Intl Journal of Cancer

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Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

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“…For example, the studies from our laboratory considered 95 genetically enriched BC cases, which were negative for known breast cancer predisposing mutations. We subjected to full-length sequencing 22 DNA repair genes and revealed a role of truncating mutations of BLM gene in breast cancer predisposition [9,140]; importantly, these findings were later replicated in independent studies [25,26]. There are somewhat more robust investigations involving several hundreds of high-risk BC patients; they reported the identification of several new BC genes; however, they did not communicate the overall number of genes tested [124,130].…”

Section: Breast Cancermentioning

confidence: 91%

Identification of novel hereditary cancer genes by whole exome sequencing

et al. 2015

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Whole exome sequencing (WES) provides a powerful tool for medical genetic research. Several dozens of WES studies involving patients with hereditary cancer syndromes have already been reported. WES led to breakthrough in understanding of the genetic basis of some exceptionally rare syndromes; for example, identification of germ-line SMARCA4 mutations in patients with ovarian hypercalcemic small cell carcinomas indeed explains a noticeable share of familial aggregation of this disease. However, studies on common cancer types turned out to be more difficult. In particular, there is almost a dozen of reports describing WES analysis of breast cancer patients, but none of them yet succeeded to reveal a gene responsible for the significant share of missing heritability. Virtually all components of WES studies require substantial improvement, e.g. technical performance of WES, interpretation of WES results, mode of patient selection, etc. Most of contemporary investigations focus on genes with autosomal dominant mechanism of inheritance; however, recessive and oligogenic models of transmission of cancer susceptibility also need to be considered. It is expected that the list of medically relevant tumor-predisposing genes will be rapidly expanding in the next few years.

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Candidate gene analysis of BRCA1/2 mutation-negative high-risk Russian breast cancer patients

Cited by 33 publications

References 24 publications

Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network

Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer

Identification of novel hereditary cancer genes by whole exome sequencing

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