Pathology & Oncology Research

, Volume 24, Issue 3, pp 477–481 | Cite as

Intratumoral Heterogeneity of Frameshift Mutations of GLI1 Encoding a Hedgehog Signaling Protein in Colorectal Cancers

  • Ju Hwa Lee
  • Sang Yong Song
  • Min Sung Kim
  • Nam Jin Yoo
  • Sug Hyung LeeEmail author
Original Article


GLI1 is a transcription factor for hedgehog signaling that plays a crucial role in signaling pathways for controlling cell proliferation, alterations of which are known to contribute to tumorigenesis. Aim of this study was to explore whether GLI1 gene is mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that GLI1 had a G7 mononucleotide repeat in the coding sequences that could be a mutation target in the cancers with microsatellite instability (MSI). In this study, we analyzed frameshift mutation of GLI1 in 79 GCs and 129 CRCs (high MSI (MSI-H) or microsatellite stable (MSS)) by single-strand conformation polymorphism analysis and DNA sequencing. We found 10 frameshift mutations in the repeat, nine for CRCs and one for GC. All of the mutations were detected in cancers with MSI-H and there was a statistical difference in the frameshift mutation frequencies between the cancers with MSI-H (10/113) and MSS (0/90). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the mutations exhibited regional ITH in three of the CRCs (18.8%). Our data indicate GLI1 harbored not only frameshift mutation but also its mutational ITH, which together could be a feature of GC and CRC with MSI-H.


GLI1 Frameshift mutation Colon cancer Microsatellite instability Intratumoral heterogeneity 



This work was supported by a grant from National Research Foundation of Korea (2012R1A5A2047939).

Compliance with Ethical Standards

Conflicts of Interest

None to declare.


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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Ju Hwa Lee
    • 1
  • Sang Yong Song
    • 2
  • Min Sung Kim
    • 1
  • Nam Jin Yoo
    • 1
  • Sug Hyung Lee
    • 1
    Email author
  1. 1.Department of Pathology, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
  2. 2.Department of Pathology and Translational Genomics, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea

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