03 July 2020
Mutation linked to type of pancreatic tumour
Published online 5 January 2014
While pancreatic cancer is not a common cancer, it is one of the most lethal forms of the disease: only 6% of patients survive for longer than five years. Researchers have now found a genetic mutation that causes one type of pancreatic tumour, known as a functional pancreatic neuroendocrine tumour (PNET).
The team, which included Jun Wang from King Abdulaziz University in Jeddah, Saudi Arabia, sequenced the coding region of the genome of tumour cells taken from 10 patients with an insulinoma, a type of PNET that can lead to unchecked insulin release and hypoglycaemia, and published their finding in Nature Communications.
Several of the samples had a mutated version of Yin Yang 1 (YY1), a widely-expressed transcription factor involved in many biological processes, including glucose metabolic homoeostasis. The researchers then screened 103 more samples and found the mutation in 31, confirming a role for YY1 in insulinoma.
This is the first mutation linked to functional PNETs, a discovery that could improve the detection and treatment of such cancers. The position of the mutation in the gene suggests that it affects YY1's ability to repress other genes. To confirm this, the researchers measured the expression level of several YY1 targets and found that they were indeed upregulated in insulinomas.
"Identifying an oncogene which plays a role in the development of insulinomas may help identify novel targets for therapeutic intervention against this highly morbid disease," says Guang Ning, the senior author of the study.
- Cao, Y. et al. Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1. Nature Communications (2013) doi:10.1038/ncomms3810