2023 World Conference on Lung Cancer (Posters)-EP02.03. Defining Genetic Instability at Tetranucleotide Repeats (EMAST) In a Non-small Cell Lung Cancer

EP02.03. Defining Genetic Instability at Tetranucleotide Repeats (EMAST) In a Non-small Cell Lung Cancer - PDF(Slides)

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Researchers at the University of Technology Sydney (UTS) have been studying the relationship between genetic instability at tetranucleotide repeats (EMAST) and non-small cell lung cancer (NSCLC). EMAST is a result of defective DNA repair in cancer and involves the insertion or deletion of 4-nucleotide repeats in DNA sequences. The researchers aimed to develop a diagnostic biomarker test for EMAST in NSCLC and determine how it is associated with changes in the MSH3 protein.<br /><br />The study found that 30% of NSCLC patients had EMAST-positive tumors. Squamous cell carcinoma had the highest prevalence of EMAST. Immunohistochemistry staining showed a patchy loss of MSH3 staining, which correlated with EMAST positivity. The researchers also analyzed data from the TCGA PanCancer Atlas and found that shallow deletions of the MSH3 gene were common in squamous cell carcinoma but less common in adenocarcinoma. However, reduced mRNA expression of MSH3 was similar in both cancer types.<br /><br />The study concluded that coding sequence alterations or reduced mRNA expression of the MSH3 gene are less common than EMAST in lung cancer. Shallow deletions of MSH3 are associated with reduced mRNA expression but their association with EMAST is unknown. EMAST may be associated with a functional defect and mislocalization of the MSH3 protein in lung cancer. Detecting MSH3 protein dysfunction through EMAST or immunohistochemistry may help identify lung cancers responsive to drugs that target DNA repair defects.<br /><br />Overall, this study provides insights into the relationship between EMAST and MSH3 protein dysfunction in NSCLC and suggests that EMAST could be a potential surrogate biomarker for MSH3 dysfunction. Further research is needed to fully understand the role of MSH3 in EMAST and its implications for NSCLC treatment.

Asset Subtitle

Hannah Parker

Meta Tag

Speaker Hannah Parker

Topic Tumor Biology: Preclinical Biology - Regulatory Mechanisms

Keywords

EMAST

NSCLC

genetic instability

MSH3 protein

squamous cell carcinoma

immunohistochemistry staining

TCGA PanCancer Atlas

mRNA expression

lung cancer

DNA repair