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Intratumoral Heterogeneity of Somatic Mutations for NRIP1, DOK1, ULK1, ULK2, DLGAP3, PARD3 and PRKCI in Colon Cancers

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Pathology & Oncology Research

Abstract

Both NRIP1 and DOK1 genes are considered candidate tumor suppressor genes (TSGs). Also, cell polarity-related genes PARD3, PRKCI and DLGAP3, and autophagy-related genes ULK1 and ULK2 genes are considered to play crucial roles in tumorigenesis. The aim of our study was to find whether these genes were mutated in colorectal cancer (CRC). In a genome database, we observed that each of these genes harbored mononucleotide repeats in the coding sequences, which could be mutated in cancers with high microsatellite instability (MSI-H). For this, we studied 124 CRCs for the frameshift mutations of these genes and their intratumoral heterogeneity (ITH). NRIP1, DOK1, PARD3, PRKCI, DLGAP3, ULK1 and ULK2 harbored 18 (22.8%), 2 (2.5%), 2 (2.5%), 2 (2.5%), 5 (6.3%), 2 (2.5%) and 2 (2.5%) of 79 CRCs with MSI-H, respectively. However, we found no such mutations in microsatellite stable (MSS) cancers in the nucleotide repeats. We also studied ITH for the frameshift mutations in 16 cases of CRCs and detected that the frameshift mutations of NRIP1, DOK1, PARD3, PRKCI, DLGAP3, ULK1 and ULK2 showed regional ITH in 5 (31.3%), 2 (12.5%), 0 (0%), 0 (0%), 1 (6.3%), 1 (6.3%) and 3 (18.8%) cases, respectively. Our data exhibit that candidate cancer-related genes NRIP1, DOK1, PARD3, PRKCI, DLGAP3, ULK1 and ULK2 harbor mutational ITH as well as the frameshift mutations in CRC with MSI-H. Also, the results suggest that frameshift mutations of these genes might play a role in tumorigenesis through their inactivation in CRC.

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Acknowledgements

This study was supported by grants from National Research Foundation of Korea (2012R1A5A2047939 and 2016R1D1A1B01007490).

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Author notes

  1. Eun Ji Choi and Ju Hwa Lee contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea

    Eun Ji Choi, Ju Hwa Lee, Min Sung Kim, Nam Jin Yoo & Sug Hyung Lee

  2. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Sang Yong Song

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  1. Eun Ji Choi
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Correspondence to Sug Hyung Lee.

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Choi, E.J., Lee, J.H., Kim, M.S. et al. Intratumoral Heterogeneity of Somatic Mutations for NRIP1, DOK1, ULK1, ULK2, DLGAP3, PARD3 and PRKCI in Colon Cancers. Pathol. Oncol. Res. 24, 827–832 (2018). https://doi.org/10.1007/s12253-017-0297-0

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  • DOI: https://doi.org/10.1007/s12253-017-0297-0

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