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Updated: Nov 9, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in squamous cell lung cancer
Ilenia Chatziandreou1, Adriana Psaraki1, Konstantinos Paschidis1
11(st) Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str., 11527, Goudi, Athens, Greece.
Abstract:
Non-small cell lung cancer (NSCLC) targeted therapies are mostly based on activating mutations and rearrangements which are rare events in Lung Squamous Cell Carcinomas (LUSC). Recently advances in immunotherapy have improved the therapeutic repository for LUSC, but there is still an urgent need for novel targets and biomarkers. We examined 73 cases of LUSC for relative copy number amplification of DCUN1D1, BCL9, FGFR1 and ERBB2 genes and searched for correlations with molecular alterations and clinicopathological characteristics. In our cohort BCL9 gene was amplified in 57.5 % of the cases, followed by DCUN1D1 in 37 %, FGFR1 in 19 % whereas none of the cases were amplified in ERBB2 gene. The majority of the samples exhibited amplification in at least one gene while half of them displayed concurrent amplification of two/three genes. Interestingly, 93 % of the FGFR1 amplified cases were also found co amplified with DCUN1D1 and/or BCL9 genes. Linear correlations were found between BCL9 and DCUN1D1 as well as BCL9 and FGFR1 gene amplification. BCL9 and DCUN1D1 genes' amplification was correlated with poorly differentiated tumors (p = 0.035 and p = 0.056 respectively), implying their possible role in tumor aggressiveness. This is the first study, to the best of our knowledge that examines the correlation of DCUN1D1 and BCL9 genes relative copy number amplification with molecular alterations and clinicopathologic characteristics of squamous cell lung cancer tissue samples. Our findings show concurrent amplification of genes in different chromosomes, with possible involvement in tumor aggressiveness. These results support the complexity of LUSC tumorigenesis and imply the necessity of multiple biomarkers / targets for a more effective therapeutic result in LUSC.
Insights
Gene amplifications in Lung Squamous Cell Carcinoma (LUSC) like BCL9 and DCUN1D1 correlate with aggressive tumors. This highlights the need for multiple biomarkers and targets for effective LUSC therapy.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Targeted therapies for non-small cell lung cancer (NSCLC) primarily focus on mutations and rearrangements, which are infrequent in Lung Squamous Cell Carcinomas (LUSC).
- While immunotherapy has advanced LUSC treatment, novel therapeutic targets and biomarkers remain critical.
- Understanding genetic alterations in LUSC is essential for developing new treatment strategies.
Purpose of the Study:
- To investigate the relative copy number amplification of DCUN1D1, BCL9, FGFR1, and ERBB2 genes in LUSC.
- To explore correlations between these gene amplifications and molecular alterations.
- To examine the relationship between gene amplifications and clinicopathological characteristics in LUSC.
Main Methods:
- Analysis of 73 LUSC tissue samples.
- Quantitative assessment of relative copy number amplification for DCUN1D1, BCL9, FGFR1, and ERBB2 genes.
- Statistical analysis to identify correlations with molecular alterations and clinicopathological features.
Main Results:
- BCL9 gene amplification occurred in 57.5% of cases, DCUN1D1 in 37%, and FGFR1 in 19%; ERBB2 amplification was not observed.
- Most samples showed amplification in at least one gene, with 50% exhibiting concurrent amplification of two or three genes.
- FGFR1 amplification frequently co-occurred (93%) with DCUN1D1 and/or BCL9. BCL9 and DCUN1D1 amplifications correlated with poorly differentiated tumors, suggesting a role in tumor aggressiveness.
Conclusions:
- Concurrent gene amplifications across different chromosomes are observed in LUSC, potentially influencing tumor aggressiveness.
- Amplification of BCL9 and DCUN1D1 genes is associated with poorly differentiated LUSC, indicating their potential role in tumor progression.
- These findings underscore the genetic complexity of LUSC tumorigenesis and the necessity of utilizing multiple biomarkers and targets for improved therapeutic outcomes.
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