Notch1 And Its Ligand Of Jag1 Gene Methylation Role Of Onset In Mammary Gland Carcinoma And Difference Between Uygur And Han Women In Xinjiang

Objective:Notch1 and its ligand JAG1 gene methylation may play a significant part in the tumorigenesis and the development. The study that to exploring Notch1 and JAG1 gene methylation role of onset in mammary gland carcinoma and difference between Uygur and Han Women in XinJiang.Methods:The methylation of Notch1 and JAG1 gene in Uygur and Han women breast invasive ductal carcinoma (IDC;n=75,89),ductal carcinoma in situ(DCIS;n=11,20), atypical ductal hyperplasia(ADH; n=5,11), and usual ductal hyperplasia (UDH;n=27,20)were quantitative detection by MassARRY. Apply hierarchical cluster analysis which two genes individual CpG units methylation rate in all lacteal gland samples by Cluster3.0 and Eisensoftware TreeView software. All of the methylation data were analyzed by using the SPSS 17.0 software package.Results:(1) Our results showed that the analyzed regions of the Notch 1 gene contained 14 CpG units (total of 1,666 analyzed units in 119 Uigur samples and 1,960 analyzed units in 140 Han samples). The mean methylation levels of Notchl gene CpG₃,4.5,8 in han samples and CpG₁.2,3,4.5,8 and so on in Uygur samples were significantly lower in IDC than else three group (P<0.0083). The mean methylation states of CpG₄.5,10.11,14.15.16 sites of han and CpG₁0.11 sites of Uygur in breast caner between axillary node metastasis and without axillary node metastasis, and CpG₁4.15.16,18 sites of han and CpG₁.2 sites of Uygur in different clinical stage of TNM, and CpG₁.2,12.13 sites of han and CpG₉ sites of Uygur in different grades of pathohistology, and CpG₃,8,14.15.16 sites of han and CpG 1.2 sites of Uygur between ER(+),PR(+),C-erbB-2 (-) and ER (-),PR (-),C-erbB-2(+) had significant statistics difference(P<0.05) (2) The analyzed promoter region of JAG 1 gene contained 15 CpG units (total of 1,785 analyzed units in 119 Uigur samples and 2,100 analyzed units in 140 Han samples). The mean methylation rates of JAG1 gene CpG₂,6,13,16.17,26 sites of in IDC group was lower than UDH group in Han samples and CpG₁1.12 sites in IDC group was lower than UDH, DCIS group in Uygur samples.The mean methylation levels of CpG₈.9.10 sites between axillary node metastasis and without axillary node metastasis of Uygur and han breast caner, and CpG₈.9.10,23.24.25 sites of han and CpG₁6.17 sites of Uygur in different clinical stage of TNM, and CpG 11.12 sites of han and CpG₁ sites of Uygur in different grades of pathohistology, and CpG₁3,26 sites of Uygur between ER(+), PR(+), C-erbB-2(-) and ER (-),PR (-),C-erbB-2(+) had significant statistics difference(P<0.05). (3)The mean methylation rates of identical CpG units Notch1 and JAG1 gene in Uygur IDC were generally higher than han people(P<0.05).Conclusions:(1)These result indicate that the alteration generally hypomethylation of Notch1 and JAG1 gene in breast cancer, but its expression levels of mRNA and protein were heightened.This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notchl and its ligand JAG1, and this change may have important significance in breast tumorigenesis and the development.(2) The CpG₃,4.5,8 sites of Han and CpG₁.2,3,4.5,8 and so on sites of Uygur hypomethyl ation of Notch1 gene and the CpG₂,6,13,16.17,26 sites of Han and CpG₁1.12 sites of Uygur hypomethylation of JAG1 gene are associated with breast carcinogenesis; and both co-participation in tumorigenesis and the development of Han and Uygur from lacteal gland benign lesions to breast cancer (3) The mean methylation levels of Notchl and JAG1 gene of alike CpG units in Uygur IDC were generally higher than han people.(4)The promoter hypomethylation of Notchl and JAG1 difference in quantity of CpG units between Uygur and han women which presentation nation variability of methlation pattern.