title: Expression levels of HER2/neu and those of collocated genes at 17q12-21,             in breast cancer.
abstract: HER2/neu is associated with poorer clinical outcome in breast cancer. Expression             patterns of co-localised cancer-associated genes at 17q12-21 were examined using             RT-PCR. The study group consisted of a 96-patient cohort. Relative quantity of             mRNA expression was calculated using the comparative cycle threshold method and             Qbase software. Results were analysed to detect expression patterns among the             genes, and to identify associations between expression levels and clinical data.             Levels of HER2/neu correlated with those of GRB7 (r=0.551, p<0.001), RARA (r=0.391,             p<0.001), RPL19 (r=0.549, p<0.001) and LASP1 (r=0.399, p<0.001). GRB7             was significantly inversely associated with improved DFS at 60 months (p=0.036).             RARA levels were greater in HER2/neu-positive as opposed to HER2/neu-negative             patients (p=0.021); levels were significantly higher in ER-positive patients,             relative to those who were ER-negative (p=0.003). Levels of RPL19 were significantly             higher in the HER2/neu-overexpressing (p=0.010) and luminal B subtypes (p=0.007).             LASP1 levels were higher in those patients who had been classified clinically             as HER2/neu-positive (p=0.004). This study reaffirms the correlation between HER2/neu             and the co-localised LASP1 and GRB7; the latter target may hold additional significance             in addition to being a surrogate marker for HER2/neu expression. The relationship             identified between RARA and ER-positivity may herald an avenue for targeted therapy             of these tumours.
authors.affiliation: Department of Surgery, Clinical Science Institute, National University                     of Ireland, Galway, Ireland.
authors.forename: Ronan W
authors.initials: RW
authors.lastname: Glynn
authors.forename: Nicola
authors.initials: N
authors.lastname: Miller
authors.forename: Sarah
authors.initials: S
authors.lastname: Mahon
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kerin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D051382:GRB7 Adaptor Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D051382:GRB7 Adaptor Protein; D060588:LIM Domain Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D012269:Ribosomal Proteins; D014404:Tubulin; C495955:GRB7 protein, human; C096353:LASP1 protein, human; C489092:RPL19 protein, human; C508053:ERBB2 protein, human