Frameshift mutations in mammalian target of rapamycin pathway genes and their regional heterogeneity in sporadic colorectal cancers

Human Pathology
Mi Ryoung ChoiSug Hyung Lee

Abstract

Mammalian target of rapamycin (mTOR) pathway is known to be involved in cancer pathogenesis. The aim of our study was to find whether mTOR-related genes were mutated and expressionally altered in colorectal cancers (CRCs). Through public database searching, we found that PIK3CB, insulin receptor substrate 1/2 (IRS1), RPS6, EIF4B, RPS6KA5, and PRKAA2 that were known as mTOR-related genes possessed mononucleotide repeats in DNA coding sequences that could be mutated in cancers with microsatellite instability (MSI). We analyzed 124 CRCs by single-strand conformation polymorphism analysis and DNA sequencing and found 7 (8.9%), 8 (10.1%), and 3 (3.8%) of 79 CRCs with high MSI that harbored IRS1, EIF4B, and RPS6KA5 frameshift mutations, respectively. These mutations were not identified in stable MSI/low MSI (0/45). In addition, we analyzed intratumoral heterogeneity (ITH) of PIK3CB, IRS1, RPS6, EIF4B, RPS6KA5, and PRKAA2 frameshift mutations in 16 CRCs and found that IRS1, EIF4B, and RPS6KA5 mutations had regional ITH in 2, 2, and 1 CRCs, respectively. We also analyzed IRS1 expression in the CRCs by immunohistochemistry. Loss of IRS1 expression was identified in 31% of the CRCs. The loss of expression was more common in those with IR...Continue Reading

References

Feb 19, 2004·Journal of the National Cancer Institute·Asad UmarSudhir Srivastava
Dec 30, 2004·Nature Genetics·Ken InokiKun-Liang Guan
Jul 7, 2007·Cancer Cell·David A Guertin, David M Sabatini
Dec 8, 2009·The Journal of Pathology·Yoo Ri KimSug Hyung Lee
Mar 4, 2010·The Journal of Pathology·Min Sung KimSug Hyung Lee
Feb 22, 2012·Histopathology·Nam Jin YooSug Hyung Lee
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·D Grahame HardieSimon A Hawley
Apr 20, 2012·Nature Reviews. Cancer·Andriy MarusykKornelia Polyak
Apr 26, 2012·International Journal of Cancer. Journal International Du Cancer·Eun Mi JeSug Hyung Lee
Sep 3, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hamidreza Montazeri AliabadiHasan Uludağ
Nov 30, 2013·Pathology, Research and Practice·S ZiadiM Trimeche
May 2, 2014·Frontiers in Oncology·Camillo PortaAlessandra Mosca
Sep 27, 2014·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Mi Ryoung ChoiSug Hyung Lee

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