Page 45 - SDIR5 Abstract book 21 12 2021.
P. 45

POSTER PRESENTATIONS



               P5



                     Intratumor heterogeneity of microsatellite instability in sporadic colorectal cancer

                                              1
                                                            2
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                                                                          1
                                Anamarija Salar , Arijana Pačić , Tamara Čačev , Sanja Kapitanović
                 1 Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bosković Institute, Zagreb, Croatia
                                  2 Department of Pathology, Clinical Hospital Dubrava, Zagreb, Croatia

               Background: Microsatellite instability (MSI) status has become an important factor in colorectal cancer
               (CRC)  therapeutic  decisions  due  to  novel  targeted  therapies  including  immune  checkpoint  inhibitors.
               Recently,  a  new  form  of  microsatellite  instability,  elevated  microsatellite  instability  at  selected
               tetranucleotides  (EMAST)  has  been  described  leading  to  possible  speculations  about  its  role  in  CRC
               development  and  progression.  Intratumor  heterogeneity  (ITH)  is  a  phenomenon  that  arises  from
               evolutionary dynamic of tumor progression leading to the clonal expansion of different clones within the
               tumor with different responses to antitumor therapy. Previous CRC heterogeneity studies have mainly
               focused on major mutations such as KRAS and TP53 while the data regarding the microsatellite instability
               is scarce. Materials and methods: In this study we have examined the possible ITH of MSI/EMAST status in
               30  sporadic  CRCs.  In  four  tumor  sections  and  corresponding  normal  mucous  tissue  MSI  status  was
               examined  using  the  conventional  Bethesda  panel  while  EMAST  status  was  established  using  five
               tetranucleotide microsatellite markers (MYCL1, D2S82, D2S85, D8S321 and D9S252). Targeted loci were
               amplified by PCR and analyzed either by polyacrylamide gel electrophoresis or GeneScan analysis. Results:
               In  MSI  and  EMAST  positive  tumors  instability  was  present  in  all  tumor  specimens,  but  with  different
               instability profiles in one tumor. Tumors positive only for EMAST presented with more uniform pattern.
               The most unstable markers were D17S250, MYCL1 and D20S82. Conclusion: In this preliminary study we
               have shown that MSI affects the ITH profile of MSI/EMAST positive tumors.
               Keywords: colorectal cancer, microsatellite instability, MSI, EMAST, tumor heterogeneity

















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