Abstract
Many genes act as both tumor suppressor gene (TSG) and proto-oncogene depending on cellular context and cancer type. Nemo-like kinase (NLK) encoding a serine/threonine kinase, Yin Yang 1 (YY1) encoding a zinc-finger transcription factor and PA2G4 encoding an ErbB3 binding protein have both of these two opposing functions. In the present study, we analyzed NLK, YY1 and PA2G4 frameshift mutations in sporadic GC and CRC with high microsatellite instability (MSI-H). Also, regional intratumoral heterogeneity (ITH) of frameshift mutations of these genes was analyzed in CRCs. We found frameshift mutations of NLK, YY1 and PA2G4 in CRC and GC with MSI-H (17/132: 12.9%), but not in those with MSS (0/90). Two (12.5%), one (6.3%) and one (6.3%) CRC (s) of the 16 CRCs exhibited ITH of NLK, YY1 and PA2G4 mutations among the 4–7 regions, suggesting that ITH of the frameshift mutations might be frequent in the CRCs. These results suggest that frameshift mutations of NLK, YY1 and PA2G4 along with the ITH might contribute to MSI-H cancer pathogenesis.
References
Shen L, Shi Q, Wang W (2018) Double agents: genes with both oncogenic and tumor-suppressor functions. Oncogenesis 7:25
Eskelinen EL (2011) The dual role of autophagy in cancer. Curr Opin Pharmacol 11:294–300
Li SZ, Zeng F, Li J, Shu QP, Zhang HH, Xu J, Ren JW, Zhang XD, Song XM, Du RL (2018) Nemo-like kinase (NLK) primes colorectal cancer progression by releasing the E2F1 complex from HDAC1. Cancer Lett 431:43–53
Hays E, Bonavida B (2019) YY1 regulates cancer cell immune resistance by modulating PD-L1 expression. Drug Resist Updat 43:10–28
Nguyen DQ, Hoang DH, Nguyen Vo TT, Huynh V, Ghoda L, Marcucci G, Nguyen LXT (2018) The role of ErbB3 binding protein 1 in cancer: friend or foe? J Cell Physiol 233:9110–9120
Imai K, Yamamoto H (2008) Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680
Choi EJ, Kim MS, Song SY, Yoo NJ, Lee SH (2017) Intratumoral heterogeneity of Frameshift mutations in MECOM gene is frequent in colorectal cancers with high microsatellite instability. Pathol Oncol Res 23:145–149
Acknowledgements
This work was supported by a grant from National Research Foundation of Korea (2019R1A5A2027588).
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Son, H.J., Choi, E.J., Yoo, N.J. et al. Somatic Mutations and Intratumoral Heterogeneity of Cancer-Related Genes NLK, YY1 and PA2G4 in Gastric and Colorectal Cancers. Pathol. Oncol. Res. 26, 2813–2815 (2020). https://doi.org/10.1007/s12253-019-00785-z
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DOI: https://doi.org/10.1007/s12253-019-00785-z