title: Loss of NF2/Merlin expression in advanced sporadic colorectal cancer.
abstract: OBJECTIVE
  NF2/Merlin was first identified through its association with neurofibromatosis type 2 (NF2). However, accumulating evidence suggests a more general involvement in tumorigenesis and, in particular, a broader role in tumor suppression. The aim of this study was to examine NF2/Merlin involvement in sporadic colorectal cancer.
  
  
  METHODS
  This study is the first to examine the role of NF2/Merlin in sporadic colorectal cancer through LOH analysis at the NF2 locus and mRNA expression analysis via quantitative RT-PCR of total NF2, NF2 isoform I and II. In addition, Merlin protein expression was assessed by immunohistochemistry and Western blotting.
  
  
  RESULTS
  NF2 LOH was detected in 20.0 % of heterozygous cases and was found to be more frequent in tumors larger than 5 cm in diameter (p = 0.041) and in tumors with a less differentiated phenotype (p = 0.027). No differences were observed in total NF2 and NF2 isoform I/isoform II mRNA expression between the tumors and their corresponding normal mucous tissues. NF2 isoform II was the most predominant isoform in all samples analyzed. mRNA expression levels of total NF2 and isoforms I and II were significantly lower in poorly differentiated tumors (p = 0.033, p = 0.036 and p = 0.044, respectively). Weak Merlin immunostaining was more frequent in poorly differentiated tumors (p = 0.034) and tumors classified as Dukes' C (p = 0.023). A distinct pattern of Merin phosphorylation was observed in tumors compared to normal mucous tissues.
  
  
  CONCLUSIONS
  Our data indicate that NF2/Merlin may serve as a potential target in the management of colorectal cancer.
authors: Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia, tcacev@irb.hr.
authors: Tamara
authors: T
authors: Cačev
authors: Gorana
authors: G
authors: Aralica
authors: Božo
authors: B
authors: Lončar
authors: Sanja
authors: S
authors: Kapitanović
mesh_terms: D000368:Aged; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D009367:Neoplasm Staging; D025581:Neurofibromin 2 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D025581:Neurofibromin 2; D020033:Protein Isoforms