Nature Cancer of Sichuan University: First elucidation of the molecular regulatory mechanism of epigenetic reprogramming of small cell lung cancer metastasis

On April 21, the team of Professor Chen Chong of the State Key Laboratory of Biotherapy and the team of the Department of Thoracic Oncology published a research paper "KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming" in Nature Cancer, which clarified for the first time histone methyl Deletion of the transferase KMT2C promotes an epigenetic mechanism of distant metastasis in small cell lung cancer (SCLC) through histone-DNA synergistic hypomethylation

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SCLC is a highly malignant neuroendocrine tumor, with an incidence of about 15-20% of the total number of lung cancers, and its 5-year survival rate is less than 10%

Based on the SCLC model, the team constructed a molecular pathway for SCLC metastasis through single-cell sequencing and collaborative analysis of clinical big data, and found that KMT2C is a key gene for SCLC metastasis, and its expression is gradually down-regulated along the SCLC metastasis pathway, and in distant There is a higher frequency of mutations in SCLC patients with terminal metastases

The team further used epigenetic-related multi-omics combined analysis and biological function research to find that the DNA methyltransferase DNMT3A in SCLC is one of the downstream genes directly regulated by KMT2C.

The scientific significance and innovation of this work lie in: (1) A primary, in situ, and clear SCLC mouse model was constructed

The research team expects that KMT2C can be used as a new molecular marker to provide an important reference for the clinical diagnosis of SCLC patients.

In recent years, the Department of Thoracic Oncology has cooperated closely with the team of Professor Chen Chong of the State Key Laboratory of Biotherapy, dedicated to the development of new targets for SCLC and the validation of new therapies

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