• Fulltext

       

        Click here to view fulltext PDF


      Permanent link:
      https://www.ias.ac.in/article/fulltext/jgen/095/03/0551-0563

    • Keywords

       

      breast cancer; alterations of SLIT2–ROBO1 signalling; active CDC42; pSer71-CDC42 .

    • Abstract

       

      The aim of the study was to understand the role of SLIT2–ROBO1/2–CDC42 signalling pathways in development of breast cancer (BC). Primary BC samples (n = 150), comprising of almost equal proportion of four subtypes were tested for molecular alterations of SLIT2, ROBO1, ROBO2 and CDC42, the key regulator genes of this pathway. Deletion and methylation frequencies of the candidate genes were seen in the following order: deletion, SLIT2 (38.6%) > ROBO1 (30%)> ROBO2 (7.3%); methylation, SLIT2 (63.3%) > ROBO1 (26.6%) >ROBO2 (9.3%). Majority (80%, 120/150) of the tumours showed alterations (deletion/methylation) in at least one of the candidate genes. Overall, alterations of the candidate genes were as follows: SLIT2, 75.3% (101/150); ROBO1, 45.3% (68/150); ROBO2, 15.3% (23/150). Significantly, higher alteration of SLIT2 locus was observed in triple negative breast cancer (TNBC) over HER2 subtype (P = 0.0014). Similar trend is also seen in overall alterations of SLIT2 and/or ROBO1, in TNBC than HER2 subtype (P = 0.0012); of SLIT2 and/or ROBO2 in TNBC than luminal A (P = 0.014) and HER2 subtype (P = 0.048). Immunohistochemical analysis of SLIT2, ROBO1/2 showed reduced expression, concordant with their molecular alterations. Also, high expression of total CDC42 (49/52; 94.2%) and reduced expression of phospho Serine-71 CDC42 (41/52; 78.8%) was observed. Coalterations of SLIT2 and/or ROBO1, SLIT2 and/or ROBO2 had significant association with reduced expression of phospho Serine-71 CDC42 (P = 0.0012–0.0038). Alterations of SLIT2 and/or ROBO1, reduced expression of phospho Serine-71 CDC42 predicted poor survival of BC patients. Results indicate the importance of SLIT2–ROBO1–CDC42 signalling pathway in predicting tumour progression.

    • Author Affiliations

       

      RITTWIKA BHATTACHARYA1 NUPUR MUKHERJEE1 HEMANTIKA DASGUPTA1 MD. SAIMUL ISLAM1 NEYAZ ALAM2 ANUP ROY3 PRIYOBRATA DAS4 SUSANTA ROY CHOUDHURY5 CHINMAY KUMAR PANDA1

      1. Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India
      2. Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata 700 026, India
      3. Department of Pathology, North Bengal Medical College and Hospital, 734 012, Siliguri, India
      4. Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata 700 016, India
      5. Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata 700 032, India
    • Dates

       
    • Supplementary Material

       
  • Journal of Genetics | News

    • Editorial Note on Continuous Article Publication

      Posted on July 25, 2019

      Click here for Editorial Note on CAP Mode

© 2017-2019 Indian Academy of Sciences, Bengaluru.