Shanghai Jiaotong University Yangtze River Scholar Nature Sub-Journal published new sequencing results

Researchers from the Shanghai Jiaotong University School of Medicine and the BGI Research Institute have identified frequent mutations of the YY1 gene T372R by sequencing the whole exome of insulinoma. This research result was published online on December 10 "Nature Communications" (Nature Communications) magazine.

Leading this research is Guang Ning, deputy dean of Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine and a distinguished professor of Yangtze River (Guang Ning). His main research direction is clinical and basic research of metabolic syndrome; diagnosis and treatment of hereditary endocrine diseases .

Insulinoma (insulinoma), also known as pancreatic islet β-cell tumor, is a common pancreatic endocrine tumor. This disease is clinically characterized by the secretion of large amounts of insulin to cause paroxysmal hypoglycemia syndrome. Common causes. About 90% of the disease is a benign tumor of islet B cells, and about 90% is sporadic. Because there are no effective preventive measures, early detection and early diagnosis are the key to the prevention and treatment of insulinoma. Uncovering the personal genetic factors that lead to the occurrence of insulinoma is undoubtedly of great significance for early detection and diagnosis, as well as finding potential targets for treatment.

Exons are part of eukaryotic genes and contain the information needed to synthesize proteins. The human genome contains approximately 180,000 exons (about 30Mb), accounting for 1% of the human genome. All exons are called "Exome" (Exome).

Exome sequencing (Exome sequencing) is a genomic analysis method developed in recent years that uses sequence capture technology to capture and enrich DNA of whole genome exon regions for high-throughput sequencing. Because exome sequencing only requires DNA from the exon region (currently, more than 85% of diseases caused by DNA mutations are estimated to be derived from mutations in the exome region), so it is far better than sequencing the whole genome It is simple, economical and efficient, and the coverage of the target area is also higher, which is convenient for mutation detection.

At present, exon sequencing has been successfully applied in the study of Mendelian diseases such as Miller syndrome, Kabuki syndrome, and severe craniocerebral deformity. There are other cancers and complex diseases that have also been observed with highly correlated mutations using exon sequencing.

In this new article, the researchers identified the T372R frequent somatic mutations of the YY1 gene by sequencing all 10 exonic insulinomas by whole exome. Further screening in 103 additional insulinomas revealed that this hotspot mutation is present in 30% (34/113) of the tumors. In insulinoma, T372R mutation changes the expression of YY1 target gene. The researchers confirmed that the T372R mutation is clinically associated with later onset. Genotyping YY1 may help the treatment of insulinoma.

These findings indicate that YY1 plays an important role in pancreatic β cells and provides a potential therapeutic target for insulinoma.

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