Mutation Chart Of NOEY2 Gene In Breast Cancers

Objective: Breast cancer is one of the most common malignant tumors in women, and the incidence is rising, seriously threatening to women' s health. Early diagnosis and treatment is the key to breast cancer prevention. According to the modern molecular biology theory, the tumor occurrence is the result of accumulates of a series of genetics changes and the table view genetics changes, in particular, the activation of oncogenes and tumor suppressor gene inactivation. NOEY2 discovered in 1999 is a new tumor suppressor gene. The deletion of the gene, the loss of chromosome segments and the methylation of the promoter region are closely related with a variety of tumor development and transfer. It is found that the expression of NOEY2 gene is high in normal mammary epithelial cell, but decreasing or absent in breast cancer cells. Therefore, the study of expression and function of NOEY2 in breast cancer is of great significance to further understand the evolution of the molecular mechanisms in breast cancer, it also provides a new indication for early diagnosis and prognosis judging. In this study, DNA sequencing technology is used to detect the mutation of exon 1, 2 and promoter, intron, in the selected breast cancer tissue, adjacent nontumorous hyperplastic tissues and benign breast lesions, analyzing its mutation, to get gene mutation spectra and mutation hot spots in breast cancer, and to explore the role of NOEY2 mutations in breast cancer development, and this may provid important theoretical basis in revealing the molecular mechanism and early diagnosis.Methods: Fifty cases of breast cancer fresh specimens and 50 cases of benign breast lesions fresh specimens were used in this study. All the cases have been diagnosied clearly. The NOEY2 mutation of exon 1,2 and promoter, intron by polymerase chain reaction and gene sequencing techniques. Sequencing data was handled with sequence analysis software of AlignX.Results: The research results shew: (1) The mutations of promoter or/and exon2 were detected in 21 / 50 cases (42%) of breast cancer and 17/50 cases (34%) of adjacent nontumorous hyperplastic tissues and 0 / 50 cases (0%) of benign breast lesions. Mutation was not found in exonl. The same mutation of NOEY2 intron at five sites,-202T>C,-150A>T,-149T>A,-113G>C,-164insC, was detected in 50 cases of breast cancer and the adjacent nontumorous hyperplastic tissues and 50 cases of benign breast lesions, but no point mutation was detected in splice junctions. (2) The mutation spectrum was principally situated in promoter and exon2 in breast cancer and the adjacent nontumorous hyperplastic tissues. The mutations of promoter were detected in 13 cases(26%)of 50 cases of breast cancer. The mutation spectrum was from-3661 site to-3558 site. The mutation rate of-3361 site was highest(16%). In addition, the different mutations of 13 sites were detected in 13 cases respectively. The mutations of exon2 were detected in 10 cases (20%) of 50 cases of breast cancer. The mutation spectrum was from +281 site to +1110 site. The mutation rate of +735 site was highest(6%). The mutations of the noncoding region had 9 cases(18%). The mutation rate of +735 site G>A was highest, which has 3 cases(6%). In addition, the different mutations of 12 sites were detected in 12 cases respectively. The mutations of the coding region had 3 cases(6%). The samesense mutation was detected in 1 case. The frameshift mutation was detected in 3 cases. The mutations of promoter were detected in 8 cases(16%)of 50 cases of adjacent nontumorous hyperplastic tissues. The mutation spectrum was from-3661 site to-3521 site. The mutation rate of-3361 site was highest(4%). In addition, the different mutations of 12 sites were detected in 12 cases respectively. The mutations of exon2 were detected in 11 cases(22%) of 50 cases of breast cancers. The mutation spectrum was from +502 site to +1182 site. The mutation rate of +735 site was highest (6%). The mutations of the noncoding region were detected 11 cases (22%). The mutation rate of +735 site G>A was highest, which has 3 cases (6%). The mutation of +864G>A was detected in 3 cases(6%). The mutation of +1117insT was detected in 2 cases(4%). In addition, the different mutations of 14 sites were detected in 14 cases respectively. The mutation of the coding region was detected in 1 case (2%). There were 2 mutations, +502A>C, +590A>T, which were missense mutations. (3) The statistics results showed that the mutation of NOEY2 gene has no relation to onset age, histologic type, tumor size, histologic grade, clinical stage and lymph node metastasis of the breast cancer.Congclusions: (1) The mutation of NOEY2 gene is related to the occurrence of breast cancer. (2) Promoter and exon 2 of NOEY2 gene were the hot mutation spot in the breast cancer patients. (3) The mutation of NOEY2 gene has no relation to onset age, histologic type, tumor size, histologic grade, clinical stage and lymph node metastasis of the breast cancer. (4) The abnormality of NOEY2 gene has a variety of forms. To further study the mRNA and protein abnormal expression of NOEY2 gene in breast cancer tissue will help to clarify the role in the development of breast cancer.