The Mutational Hotspots Of MYBL2 In Breast Cancer

Background and ObjectiveMYBL2 is a member of MYB oncogene family, which broadly expressed in proliferating cells. B-Myb protein is an important cell cycle regulatory protein, involved in cell cycle and cell proliferation, differentiation and apoptosis. Cytogenetic analysis revealed that MYBL2 gene is associated with non-small cell lung cancer, liver cancer, ovarian cancer and prostate carcinomas. B-myb is also an important marker of poor outcome in neuroblastoma and prostate carcinomas. What's more, the level of MYBL2 expression can indicate the prognosis of breast cancer.There are few studies on the effect of MYBL2 gene mutation on the change of gene expression, however, the only studies are controversial. The reports of the mutations on MYBL2 among Asian woman are rarely seen at present.This study was designed to investigate the mutational hotspots of MYBL2 gene in breast cancer in Eastern China and the association of the mutation with the susceptibility, protein expression, clinical pathological features of breast cancer.Methods1,Sample collection:50 paraffin-embedded tissues of primary breast cancer were collected from Changhai Hospital between January 2007 and August 2009. All the cases were confirmed by operation and pathology. Other 18 paraffin-embedded tissues of the control samples taken for benign tumour specimens.2,Experimental Design:PCR amplification of exons 8 and 13 was done after extracting DNA from all paraffin-embedded samples, followed by sequencing after the product was purified. B-myb protein of breast carcinoma samples were detected by immunohistochemistry. The relationship between mutations and protein expressions, clinicalpathological parameters were analyzed, prognosis of breast cancer patients were investigated.3,Statistical analysis:Using SPSS 13.0 software. Probability values less than 0.05 were considered to indicate statistical significance. Results1,We found 14(28%) MYBL2 gene rs2070235 (A1494G) mutation in the 50 cases of breast tumor tissue. While no mutation was found in 18 benign tumour tissue. MYBL2 gene mutation in the other hotspots region of tumor and non-tumor tissues were not found.2,The B-myb protein levels in mutant genotype of MYBL2 rs2070235 (A1494G) higher than that wild genotype.3,Case study found that The mutation of MYBL2 rs2070235 (A1494G) gene has statistically significant correlation with Her-2 protein and P53 protein.ConclusionIn this study, we confirm the high frequency of MYBL2 mutation in the exon 8 rs2070235 (A1494G),which may associate with breast cancer susceptibility. The mutation correlate with high level of B-myb protein expression which confirm in vitro experiments that the mutation gene coding a more stable protein. There was significant correlation between MYBL2 gene mutation and Her2/neu,P53 expression, impling that the mutation may be indicate poorer prognosis.