Gene Mutation Identified as Diagnostic Target for Insulinoma

A recurrent mutation in the transcription factor Yin Yang 1 (YY1) is related with insulinoma oncogenesis, implicating a potential marker for the diagnosis and treatment of functional pancreatic neuroendocrine tumors (PNETs).

Functional PNETs are mainly represented by insulinoma, which secrete insulin independent of glucose and cause hypoglycemia, though the major genetic alterations in insulinomas are still unknown. Pancreatic neuroendocrine tumors are classified into functional and nonfunctional tumors by hormone secretion and clinical symptoms.


A team of scientists led by those at Shanghai Jiao-Tong University School of Medicine (China) used whole exome sequencing of 10 sporadic insulinomas to identify recurrent somatic T372R mutation in the transcription factor YY1. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis of both wild type (WT) and T372R-mutated YY1 expression in insulinomas was performed.

The team validated T372R mutation in 103 additional insulinomas samples. The results showed that 31 in 103 cases had the T372R mutation, providing evidence to support that T372R mutation is a pathogenic factor of insulinoma. In addition, they found T372R mutation could enhance the transcriptional activity of YY1. The mTOR inhibitor, which has been approved to use for cancer treatment also can regulate the transcriptional activity of YY1.

It should be noted that the T372R mutation was the first reported in public available databases such as 1,000 Genomes and dbSNP database. YY1 is a multifunctional protein, which takes part in regulating normal physiological progress such as development, differentiation, replication, and cell proliferation. It also plays an important role in regulating insulin and insulin-like growth factor (IGF) signaling that is crucial for pancreatic β-cell survival and insulin secretion. 　　

Lin Li, PhD, the project manager from the Beijing Genomics Institute (Shenzhen, China) and a coauthor said, “In this study, we conducted whole exome sequencing on sporadic insulinomas, and found the hotspot mutations of T372R in 30% insulinomas. The findings not only contribute new diagnostic and medical therapies of PNETs, but also provide new insights into diabetes studies.” The study was published on December 10, 2013, in the journal Nature Communications.

Related Links:
Shanghai Jiao-Tong University School of Medicine
Beijing Genomics Institute