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Promoter methylation and expression changes of BRCA1 in cancerous tissues of patients with sporadic breast cancer.

Li Q, Wei W, Jiang YI, Yang H, Liu J - Oncol Lett (2015)

Bottom Line: BRCA1 gene mutation is closely associated with familial hereditary breast cancer, but the BRCA1 gene mutation is rarely found in sporadic breast cancer.There was a significant statistical difference (P=0.001).BRCA1 mRNA expression was not associated with the main clinicopathologic characteristics.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Guangxi 530021, P.R. China ; Department of General Surgery, No. 303 Hospital of PLA, Nanning, Guangxi 530021, P.R. China.

ABSTRACT

BRCA1 is a susceptibility gene that has a genetic predisposition for breast cancer. BRCA1 gene mutation is closely associated with familial hereditary breast cancer, but the BRCA1 gene mutation is rarely found in sporadic breast cancer. According to previous studies, decreased expression of BRCA1 was detected in certain types of sporadic breast cancer. Aberrant methylation of DNA promoter CpG islands is one of the mechanisms by which tumor suppressor gene expression and function is lost. The aim of the present study was to investigate BRCA1 gene expression, methylation status and clinical significance in sporadic types of breast cancer. Quantitative polymerase chain reaction (PCR) and bisulfite sequencing PCR were respectively used to detect expression differences of BRCA1 mRNA and BRCA1 methylation in the 49 cancerous and paired non-cancerous samples from patients with breast cancer. The associations of BRCA1 expression and methylation status with the clinicopathologic characteristics were analysed. BRCA1 mRNA expression levels in the 49 breast cancer tissues were lower than those in the paired non-cancerous tissues. There was a significant statistical difference (P=0.001). BRCA1 mRNA expression was not associated with the main clinicopathologic characteristics. Frequency of the BRCA1 promoter methylation in the breast cancerous tissues was significantly higher than that in the non-cancerous tissues (P=0.007); BRCA1 gene methylation status was negatively correlated with mRNA expression (P=0.029); and BRCA1 methylation exhibited no association with all clinicopathological features. DNA promoter hypermethylation may be the potential mechanism accounting for BRCA1 expression silence in part of sporadic types of breast cancer. Some patients with hypermethylated BRCA1 may display favorable clinicopathological status.

No MeSH data available.


Related in: MedlinePlus

Genomic architecture of the human BRCA1 gene. (A) Location of the BRCA1 gene within human chromosome 17 (ch17 q21.31); (B) exon/intron structure of the human BRCA1 gene. Noted is the relative location of the first 1 coding exons and the translational start (ATG) codons. (C) Structure of 5′ end of BRCA1 gene. Graph of percent guanine (G) and cytosine (C) nucleotides across this region and boundaries of the CpG island. (D) Detailed information of the BRCA1 promoter region sequence. The bisulfite sequencing polymerase chain reaction primers are presented in the green shaded region. There are 14 CpG sites in this region.
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f2-ol-09-04-1807: Genomic architecture of the human BRCA1 gene. (A) Location of the BRCA1 gene within human chromosome 17 (ch17 q21.31); (B) exon/intron structure of the human BRCA1 gene. Noted is the relative location of the first 1 coding exons and the translational start (ATG) codons. (C) Structure of 5′ end of BRCA1 gene. Graph of percent guanine (G) and cytosine (C) nucleotides across this region and boundaries of the CpG island. (D) Detailed information of the BRCA1 promoter region sequence. The bisulfite sequencing polymerase chain reaction primers are presented in the green shaded region. There are 14 CpG sites in this region.

Mentions: Analysis was carried out using the Methyl Primer Express version 1.0 (Applied Biosystems) to analyze the CpG islands of the region between −2,000 and +1,000 bp, including the translational initiation codon (ATG) in detail. In the 5′ end of the BRCA1 gene, two CpG islands were revealed, a 244 bp (between −1,279 and −1,036 bp) and a 221 bp (between −937 and −717 bp) segment (Fig. 2).


Promoter methylation and expression changes of BRCA1 in cancerous tissues of patients with sporadic breast cancer.

Li Q, Wei W, Jiang YI, Yang H, Liu J - Oncol Lett (2015)

Genomic architecture of the human BRCA1 gene. (A) Location of the BRCA1 gene within human chromosome 17 (ch17 q21.31); (B) exon/intron structure of the human BRCA1 gene. Noted is the relative location of the first 1 coding exons and the translational start (ATG) codons. (C) Structure of 5′ end of BRCA1 gene. Graph of percent guanine (G) and cytosine (C) nucleotides across this region and boundaries of the CpG island. (D) Detailed information of the BRCA1 promoter region sequence. The bisulfite sequencing polymerase chain reaction primers are presented in the green shaded region. There are 14 CpG sites in this region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356378&req=5

f2-ol-09-04-1807: Genomic architecture of the human BRCA1 gene. (A) Location of the BRCA1 gene within human chromosome 17 (ch17 q21.31); (B) exon/intron structure of the human BRCA1 gene. Noted is the relative location of the first 1 coding exons and the translational start (ATG) codons. (C) Structure of 5′ end of BRCA1 gene. Graph of percent guanine (G) and cytosine (C) nucleotides across this region and boundaries of the CpG island. (D) Detailed information of the BRCA1 promoter region sequence. The bisulfite sequencing polymerase chain reaction primers are presented in the green shaded region. There are 14 CpG sites in this region.
Mentions: Analysis was carried out using the Methyl Primer Express version 1.0 (Applied Biosystems) to analyze the CpG islands of the region between −2,000 and +1,000 bp, including the translational initiation codon (ATG) in detail. In the 5′ end of the BRCA1 gene, two CpG islands were revealed, a 244 bp (between −1,279 and −1,036 bp) and a 221 bp (between −937 and −717 bp) segment (Fig. 2).

Bottom Line: BRCA1 gene mutation is closely associated with familial hereditary breast cancer, but the BRCA1 gene mutation is rarely found in sporadic breast cancer.There was a significant statistical difference (P=0.001).BRCA1 mRNA expression was not associated with the main clinicopathologic characteristics.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Guangxi 530021, P.R. China ; Department of General Surgery, No. 303 Hospital of PLA, Nanning, Guangxi 530021, P.R. China.

ABSTRACT

BRCA1 is a susceptibility gene that has a genetic predisposition for breast cancer. BRCA1 gene mutation is closely associated with familial hereditary breast cancer, but the BRCA1 gene mutation is rarely found in sporadic breast cancer. According to previous studies, decreased expression of BRCA1 was detected in certain types of sporadic breast cancer. Aberrant methylation of DNA promoter CpG islands is one of the mechanisms by which tumor suppressor gene expression and function is lost. The aim of the present study was to investigate BRCA1 gene expression, methylation status and clinical significance in sporadic types of breast cancer. Quantitative polymerase chain reaction (PCR) and bisulfite sequencing PCR were respectively used to detect expression differences of BRCA1 mRNA and BRCA1 methylation in the 49 cancerous and paired non-cancerous samples from patients with breast cancer. The associations of BRCA1 expression and methylation status with the clinicopathologic characteristics were analysed. BRCA1 mRNA expression levels in the 49 breast cancer tissues were lower than those in the paired non-cancerous tissues. There was a significant statistical difference (P=0.001). BRCA1 mRNA expression was not associated with the main clinicopathologic characteristics. Frequency of the BRCA1 promoter methylation in the breast cancerous tissues was significantly higher than that in the non-cancerous tissues (P=0.007); BRCA1 gene methylation status was negatively correlated with mRNA expression (P=0.029); and BRCA1 methylation exhibited no association with all clinicopathological features. DNA promoter hypermethylation may be the potential mechanism accounting for BRCA1 expression silence in part of sporadic types of breast cancer. Some patients with hypermethylated BRCA1 may display favorable clinicopathological status.

No MeSH data available.


Related in: MedlinePlus