Altered DNA Methyltransferase Expression in Pulmonary Large-Cell Neuroendocrine Carcinoma: Pilot Experimental Data Targeted DNMT1, DNMT3A, and DNMT3B.

[INTRODUCTION] Large cell neuroendocrine carcinoma (LCNEC) is a subtype of non-small-cell lung carcinoma with poorly understood methylation characteristics, including the activity of DNA methyltransferases. Despite the pivotal role of DNA methyltransferases in epigenetic regulation, their expression profile in LCNEC remains unexplored. This study represents the first effort to evaluate the expression of DNMT1, DNMT3A, and DNMT3B genes in patients with LCNEC.

[MATERIALS AND METHODS] We performed quantitative expression analyses of DNMT1, DNMT3A, and DNMT3B on formalin-fixed, paraffin-embedded tissue samples obtained from LCNEC patients. Normal lung tissues (n = 4) from healthy patients served as controls to determine differential expression levels.

[RESULTS] The analysis revealed upregulation of both DNMT1 and DNMT3A compared to control normal lung tissue. In addition, normalized expression values of DNMT3B were reduced compared to the analyzed DNMT1 and DNMT3A.

[CONCLUSION] In this exploratory pilot of 18 LCNEC cases, DNMT1 and DNMT3A transcripts were frequently higher relative to a normal-lung calibrator, while DNMT3B results were inconclusive due to technical limitations and small sample size. These descriptive findings warrant validation in larger, isoform-resolved cohorts before clinical inference. Future research should prioritize investigating these DNA methyltransferases to explore their therapeutic implications. Moreover, future research should also aim to detect and characterize individual DNMT3B isoforms in LCNEC patients to further elucidate their specific contributions to the pathology of the disease.