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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Genetic alterations of tumor suppressor ING1 in human non-small cell lung cancer
Zhi-Gang Luo1, Hao Tang, Bing Li
1Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
Abstract:
The aim of this study was to investigate the function of the ING1 gene in lung carcinoma. To detect the inhibitory effect of ING1 in human lung cancer, recombinant ING1b plasmids were transfected into two lung cancer cell lines with different p53 status, A549 with wild-type p53 (wtp53) and SK-MES-1 with mutant p53. Apoptosis, cell cycle, growth rate and the expression of downstream gene p21waf1 were analyzed. In addition, the complex of p33ING1b and p53 was analyzed with coimmunoprecipitation. To detect the gene alteration and the expression of ING1, 70 cases of fresh-frozen lung carcinomas and 217 cases of formalin-fixed, paraffin-embedded specimens were examined for loss of heterozygosity (LOH) and p33ING1b protein expression by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and immunohistochemistry using tissue microarrays, respectively. Overexpression of ING1b inhibited the cell growth of A549 and SK-MES-1, induced cell cycle arrest and apoptosis. p21waf1 was up-regulated and a complex of p33ING1b and wtp53 was found after transfection of ING1b in the wtp53-positive lung cancer cell. High LOH frequency was found in lung carcinomas (55.7%) and p33ING1b expression was lost in 115 of 217 carcinomas (53.0%). Furthermore, there was a highly significant inverse correlation between expression and LOH frequency (P<0.05). ING1 can inhibit the growth of lung cancer cell lines through the induction of cell cycle arrest and apoptosis by forming a complex with wtp53 and up-regulating p21waf1. In human lung cancer, expression of the ING1 gene was reduced or lost and high LOH frequency of ING1 microsatellites was found. The LOH of microsatellites may down-regulate p33ING1b and/or affect its function, thereby, contributing to lung cell carcinogenesis.
Insights
The ING1 gene inhibits lung cancer cell growth by inducing apoptosis and cell cycle arrest. Loss of ING1 gene expression and high frequency of loss of heterozygosity (LOH) were observed in lung carcinomas, suggesting its role in lung cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The ING1 gene's role in lung carcinoma is not fully understood.
- Investigating ING1's tumor suppressor function is crucial for understanding lung cancer pathogenesis.
Purpose of the Study:
- To investigate the function of the ING1 gene in lung carcinoma.
- To determine the effect of ING1 gene alteration and expression in lung cancer specimens.
Main Methods:
- Transfection of ING1b plasmids into lung cancer cell lines (A549, SK-MES-1).
- Analysis of apoptosis, cell cycle, growth rate, and p21waf1 expression.
- Coimmunoprecipitation to analyze p33ING1b and p53 complex formation.
- Loss of heterozygosity (LOH) analysis using PCR-SSCP.
- Immunohistochemistry for p33ING1b protein expression on tissue microarrays.
Main Results:
- ING1b overexpression inhibited lung cancer cell growth, induced cell cycle arrest, and apoptosis.
- p21waf1 was upregulated, and a complex of p33ING1b and wild-type p53 was observed.
- High LOH frequency (55.7%) and loss of p33ING1b expression (53.0%) were found in lung carcinomas.
- A significant inverse correlation between ING1 expression and LOH frequency was identified.
Conclusions:
- ING1 inhibits lung cancer cell growth via cell cycle arrest and apoptosis, partly through complex formation with wild-type p53 and p21waf1 upregulation.
- Reduced ING1 expression and high LOH frequency in lung carcinomas suggest ING1 inactivation contributes to lung carcinogenesis.
- LOH of ING1 microsatellites may lead to decreased p33ING1b levels or function, promoting tumor development.
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