A research team composed of Shenzhen Huada Gene Research Institute, Shenzhen Second People's Hospital (referred to as the Second Hospital of Shenzhen City) and other units, through the whole genome and whole exon sequencing research on 99 bladder cancer patient samples, found that the sister Gene mutations related to sister chromatid cohesion and segregation (SCCS) provide new ideas for the diagnosis and treatment of bladder cancer. The latest research results were published in the journal Nature Genetics on October 13, 2013.

The incidence of bladder cancer ranks first in malignant tumors of the urinary system, while in western countries its incidence is second only to prostate cancer. Transitional cell carcinoma of the bladder (TCC) is the most common histological type of bladder cancer. The incidence of males is about 3 to 4 times that of females, and it usually occurs between 40 and 70 years old. At present, the annual incidence of bladder cancer in Chinese men has reached eight in 100,000, and it is increasing year by year. For this important cancer, there is currently insufficient genomics data for researchers to develop new treatments to overcome bladder cancer.

Researchers from BGI and the Second Hospital of Beijing City performed genome-wide sequencing and all-exon sequencing on tissue samples of 99 bladder cancer patients, and found 13 important new mutant genes and 24 known mutant genes such as TP53 , HRAS, FGFR3, PIK3CA and KRAS etc. Among the new mutant genes found, the STAG2 gene located on the X chromosome is particularly special, and this gene is closely related to the SCCS process. Researchers found that the high-frequency non-synonymous mutations in the STAG2 gene occurred, and 9 of 11 samples with mutations in the gene were all terminating mutations. In addition, the ESPL1 gene associated with SCCS has also undergone high-frequency mutations.

The researchers also studied 42 pairs of tissue samples through transcriptome sequencing, and found that 32 potential gene rearrangements may lead to gene fusion, and confirmed that FGFR3 and TACC3 genes were fused. The study also found that the high expression of TACC3 was not caused by the amplification of the TACC3 gene itself, but was regulated by FGFR3, a transcriptional regulator.

In addition, the results of the study show that chromosome aneuploidy and instability are related to the occurrence of bladder cancer, and make bladder cancer the first cancer with mutations in SCCS-related genes. In addition, this study provides more comprehensive and comprehensive genomic mutation information for bladder transitional cell tumors, and proves that gene mutations can affect the SCCS process, while providing a new possibility for the diagnosis and treatment of bladder cancer.

Chen Chao, the project leader of BGI, pointed out: "In this study, we found a number of mutations related to SCCS, including high-frequency mutations of STAG2, ESPL1 genes, and FGFR3-TACC3 gene fusion. This finding confirms SCCS Related gene mutations are indeed related to the occurrence of bladder cancer, which has greatly promoted the genetic research of bladder cancer, and also provided new ideas for the diagnosis and treatment of bladder cancer. In addition, the data resources obtained in the study will also provide further insights into bladder cancer Research has laid an important scientific foundation. "

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