MUTATIONAL ANALYSIS OF AMINO TERMINAL DOMAIN OF INSULIN RECEPTOR SUBSTRATE-1 (IRS1) GENE IN GLIOBLASTOMA MULTIFORME PATIENTS


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Gülaçar İ. M. , Tülüce Y., Özkol H., Görgişen G., Yakut S.

6.Multidispliner Kanser Araştırma Kongresi, Konya, Turkey, 27 - 30 October 2016, pp.143

  • Publication Type: Conference Paper / Full Text
  • City: Konya
  • Country: Turkey
  • Page Numbers: pp.143

Abstract

Aim

In the recent studies about cancer-diabetes relations, Insulin Receptor Substrate (IRS) proteins that are mediator protein family and have pivotal roles in insulin signal pathway have become the focus of attention.  Because IRS-1 is widely expressed in human tissues and has important role in insulin signaling, it is most studied member of this protein family. Due to becoming one of targeted protein and gene in both cancer and diabetes studies; genomic changes, expression/activation profiles and functional status of IRS-1 have been studied by a lot of researchers. We have detected some mutations in carboxy terminal domain of IRS-1 in our previous study. In this study, we want to also determine presence or absence of mutation in PH (pleckstrin homology) and PTB (phosphotyrosine binding) regions that are located in amino terminal domain of this protein.

 

Material/Methods

In this study, we have isolated and sequenced genomic DNAs from tumor samples of 28 Glioblastoma Multiforme tumors and 6 control tissues were obtained by autopsy and we looked for the presence or absence of mutations in the region PH and PTB domains.

 

Results

On the basis of our results, we detected p.A124S heterozygote changes in PH domain in 1 patient and p.G234G, c.702G>A heterozygote changes in PTB region of IRS1 in 1 of 28 patient samples compare to the controls.

 

Discussion/Conclusion

PH and PTB regions have a pivotal role in activation of IRS1 and diversity of signaling. Therefore, genomic changes in these regions may lead to tumorigenesis. Our results suggest that heterozygote changes in these regions of IRS1 may be involved in the modulation of IRS1 functions and could be relevant to Glioblastoma Multiforme.