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Whole Genome Sequencing of Monozygotic Twins Discordant for Lung Fibrosarcoma Reveals SETD8 as a Tumor Participator That Promotes Faithful DNA Replication
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A7083 - Whole Genome Sequencing of Monozygotic Twins Discordant for Lung Fibrosarcoma Reveals SETD8 as a Tumor Participator That Promotes Faithful DNA Replication
Author Block: M. Li1, H. Liao2, C. Zhu1, Y. Wu1, Y. Wu1, X. Geng2, Z. Chen1, H. Shen1, S. Ying1, W. Li1; 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, 2Zhejiang University School of Medicine, Hangzhou, China.
RATIONALE : Pulmonary sarcomatous neoplasms are a rare group of tumors occur in the lung. We received a pair of monozygotic twins discordant for sarcomatoid neoplasms of the right principal bronchus in their early age, and a whole-genome sequencing suggested H4K20-specific histone methyltransferase SETD8 as a novel gene that might be linked to tumorigenesis.We aimed to determine how SETD8 acts in tumorigenesis, and the potential therapeutic relevance of targeting SETD8.
METHODS : Whole-genome sequencing was used in the twins mentioned above. Through comparison analysis among the twins and the general population, 11 genes were first screened out. After further siRNA screening of these genes, we identified setd8 as the most possible participant in tumor occurrence. Two individual siRNAs of setd8 were used in U2OS and human bronchial epithelium (HBE) cells, cell proliferation, apoptosis, ageing, cell cycle, DNA damage and replication were analyzed.
RESULTS : The silencing of SETD8 inhibited cell proliferation and increased apoptosis in both two cell lines. Cell cycle arrest and DNA damage also occurred without setd8. DNA fiber assay showed that compared with control, cells transfected with setd8 siRNA exhibited slower replication fork speed.
CONCLUSIONS: SETD8 is vital to preserve genomic integrity by promoting faithful DNA replication. Its key role in cell proliferation presents a new target for cancer therapy.
Author Block: M. Li1, H. Liao2, C. Zhu1, Y. Wu1, Y. Wu1, X. Geng2, Z. Chen1, H. Shen1, S. Ying1, W. Li1; 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, 2Zhejiang University School of Medicine, Hangzhou, China.
RATIONALE : Pulmonary sarcomatous neoplasms are a rare group of tumors occur in the lung. We received a pair of monozygotic twins discordant for sarcomatoid neoplasms of the right principal bronchus in their early age, and a whole-genome sequencing suggested H4K20-specific histone methyltransferase SETD8 as a novel gene that might be linked to tumorigenesis.We aimed to determine how SETD8 acts in tumorigenesis, and the potential therapeutic relevance of targeting SETD8.
METHODS : Whole-genome sequencing was used in the twins mentioned above. Through comparison analysis among the twins and the general population, 11 genes were first screened out. After further siRNA screening of these genes, we identified setd8 as the most possible participant in tumor occurrence. Two individual siRNAs of setd8 were used in U2OS and human bronchial epithelium (HBE) cells, cell proliferation, apoptosis, ageing, cell cycle, DNA damage and replication were analyzed.
RESULTS : The silencing of SETD8 inhibited cell proliferation and increased apoptosis in both two cell lines. Cell cycle arrest and DNA damage also occurred without setd8. DNA fiber assay showed that compared with control, cells transfected with setd8 siRNA exhibited slower replication fork speed.
CONCLUSIONS: SETD8 is vital to preserve genomic integrity by promoting faithful DNA replication. Its key role in cell proliferation presents a new target for cancer therapy.
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