Abstract 1223P
Background
Mammalian SWI/SNF complexes are ATP-dependent chromatin remodelers composed of many subunits that work together to enable a fine-tuned transcriptional regulation and genome integrity that modifies the DNA histone interactions to regulate the gene expression. Previous whole-genome studies have identified SWI/SNF subunits as major targets of mutations suggesting a remarkable implication of this complex in tumorigenesis.
Methods
To examine the mutational and expression status of the SWI/SNF complex in lung adenocarcionoma (LUAD), we performed targeted DNA sequencing and RT-qPCR in 70 LUAD primary tumor samples and 27 of the paired normal adjacent tissue samples.
Results
Twenty-nine (41.4%) of the primary tumors harbored at least one mutation in a lung SWI/SNF subunit and, underlining the importance of SWI/SNF mutations in lung cancer. As expected, SMARCA4 was the most commonly mutated SWI/SNF gene (11.4% of samples), followed by ARID1A (8.6%), ARID2 (7.1%), ARID1B (4.3%), and PBRM1 (4.3%). Given expression data, 42 tumors (60%) had more than 10 downregulated subunits. On average, each lung SWI/SNF subunit was downregulated in approximately 57% of LUAD patients.The most frequent alterations were missense mutations (65.8%) followed by stop gain (13.2%), frameshift indels (10.5%), splice site alterations (5.3%), and inframe indels (5.3%).
Conclusions
These findings argue that the high mutation rate is not the only cause that can affect the function of the SWI/SNF complex. We propose a new criterion for the classification of lung adenocarcinoma patients using the mutational profile of the lung SWI/SNF subunits.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hospital Universitario Clinico San Cecilio De Granada.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.