title: Frequent inactivation of SLIT2 and ROBO1 signaling in head and neck lesions: clinical and prognostic implications.
abstract: OBJECTIVE
  The protein SLIT2 and its receptor ROBO1 regulate different cellular processes, such as proliferation, apoptosis, and migration. In this study our aim is to understand the alterations of these genes during development of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  First, molecular alterations of the genes were analyzed in 30 dysplastic lesions, 128 primary HNSCC samples, and 1 HNSCC cell line. Then alterations were correlated with mRNA expression (n = 22) and protein expression (n = 29). Finally, the alterations were correlated with different clinicopathologic parameters and clinical outcomes of the patients.
  
  
  RESULTS
  ROBO1 had a comparatively high frequency of deletion (28.5%-54.2%) from dysplastic lesions and subsequent clinical stages than did SLIT2 (16.6-27%). On the contrary, SLIT2 had a high frequency (56.6%-81.2%) of promoter methylation from dysplastic lesions onward compared with ROBO1 (20%-32.8%). Interestingly, alterations of SLIT2 and ROBO1 were high in dysplastic lesions (80%), followed by comparable frequencies (92.5%-95.3%) in subsequent stages of tumor. Alterations of these genes showed concordance with their mRNA/protein expression and significant association with poor patient outcome.
  
  
  CONCLUSIONS
  Our data suggest that inactivation of SLIT2 and/or ROBO1 is one of the early events in development of dysplastic lesions of head and neck and has prognostic importance.
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India; Department of Molecular Biology and Biotechnology, University of Kalyani, Nadia, India.
authors.forename: Guru Prasad
authors.initials: GP
authors.lastname: Maiti
authors.affiliation: Department of Biological Science, Presidency University, Kolkata, India.
authors.forename: Amlan
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: National Brain Research Centre, Manesar, Gurgaon, Haryana, India.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Mondal
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Susmita
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chakraborty
authors.affiliation: North Bengal Medical College, Sushruta Nagar, Darjeeling, West Bengal, India.
authors.forename: Anup
authors.initials: A
authors.lastname: Roy
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychowdhury
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India. Electronic address: ckpanda.cnci@gmail.com.
authors.forename: Chinmay Kumar
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein