title: NOEY2 mutations in primary breast cancers and breast hyperplasia.
abstract: OBJECTIVE
  The NOEY2 gene mutations and protein expression in human breast cancers, adjacent breast tissues and breast benign lesions were analysed to explore the potential correlation between the mutation spectrum and breast cancer development and progression.
  
  
  METHODS
  The promoter, exon and intron regions of NOEY2 gene were amplified by polymerase chain reaction (PCR) with DNA extracted from 50 human breast cancer and corresponding adjacent breast tissues as well as 50 breast benign lesions, respectively. The PCR products were then sequenced and analysed. The effect of mutations on the expression of NOEY2 protein by immunohistochemistry were proven as well.
  
  
  RESULTS
  Twenty-one of 50 (42%) breast cancer mutations were identified in promoter (11 cases) and exon 2 (seven cases on untranslation region and three on coding region) and 17 of 50 (34%) adjacent breast tissues (all were atypical hyperplasia lesions) occurred mutations, including six promoter mutations and 11 exon 2 changes (10 cases on untranslation region and one on coding region). Interestingly, the mutations were identified in both breast cancers and the corresponding adjacent breast tissues collected from the same patient in seven of them. No mutation was identified in all benign breast tissues. Immunohistochemical analysis showed that two of 17 mutational adjacent breast tissue samples were NOEY2 immunoreaction negative, and in all 21 mutations of breast cancers five cases were of loss of NOEY2 expression. All mutations with immunoreaction negative factor were located at promoter and/or exon 2 coding region. NOEY2 gene mutations were not correlated with patient ages, histological types, tumour sizes, histological grades, clinical stages, axillary lymph node metastases or with the condition of hormone receptor (ER, PR) expression and HER2 amplification.
  
  
  CONCLUSIONS
  The mutations of human NOEY2 were identified in human breast cancers and the corresponding adjacent breast tissues. The hot mutation spots were its promoter and exon 2 regions, and those occurring at the exon2 coding region and part of the promoter may alter the expression of NOEY2. The presence of NOEY2 mutations in human breast cancer and early-stage lesions indicates that NOEY2 mutations may be partly associated with breast tumourigenesis.
authors.affiliation: Department of Pathology, Kunming General Hospital/Kunming Medical College, 212 Daguan Road, Kunming, Yunnan 650032, PR China. yangjulun@yahoo.com
authors.forename: Julun
authors.initials: J
authors.lastname: Yang
authors.forename: Aiping
authors.initials: A
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Baolin
authors.initials: B
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Wenxing
authors.initials: W
authors.lastname: Zhao
authors.forename: Wenmang
authors.initials: W
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C117386:DIRAS3 protein, human; D020741:rho GTP-Binding Proteins