3 July 2020

New method reveals common biomarker for cancer and neurodegeneration disease

A new and more precise method of sequencing mitochondrial DNA developed by researchers from Issazadeh-Navikas Group at BRIC has revealed a mutation hotspot which is associated with both neurodegeneration disease and several types of cancer, rendering it a potential biomarker. The results have just been published in EBioMedicine.

New method brought surprising results

While the majority of the human DNA is stored in the nuclei of our cells, a smaller portion of DNA material is found in the so-called mitochondria - cellular organelles responsible for converting energy from our food into energy that can be used by our cells.

Alterations in the mitochondrial DNA has been linked to age related diseases including neurodegeneration disease and in a new study, BRIC researchers set out to identify disease causing mutations in a model of Parkinson’s Disease (PD). However, since mitochondrial DNA is organized differently in the cells than cell nucleus DNA, traditional methods of sequencing cell cultures or tissue did not provide clear results. 

The researchers therefore developed a new technique to sequence mitochondrial DNA in single cells and this made them able to identify mutations present in a very small proportion of the mitochondrial DNA.  By use of the new technique the researchers discovered an area of the genome (Nd5/Nd4) which is especially prone to mutations – a so-called mutation hotspot. In order to verify the method, the researchers then performed the same type of sequencing on breast- and colon cancer cell lines as well as samples from patients with blood cancer and not only did the technique also work well here - it revealed the same mutation hotspot as in the PD disease model.

Important fundamental findings with clinical potential

By identifying the same mutation hotspot in different samples and across species, the researchers have found a common biomarker for several types of cancer and neurodegeneration diseases that can possibly be used in future diagnostics and stratification of patients with cancer and neuro disease.

Emilie Tresse-Gommeaux, author on the publication expects that the new technique with its benefits in terms of sensitivity will be used largely by the scientific community, and she stresses that the new findings are important in more ways than one:

From the perspective of fundamental biology, it is paramount to determine the mutations that are associated with neuronal cell death and the mechanisms by which these mutations alter mitochondrial function to cause neurodegeneration. Biomedically speaking, this hotspot of mutations is, in our view, an important biomarker that should be screened in cancer and neurodegeneration and tested on a larger scale.

About MitoSV-seq

Researchers use genomic sequencing to search for genetic variations that causes disease. Whereas nuclei DNA is found in one copy in each cell, the copy number of mitochondrial genomes reach several hundreds per cell, making it difficult to identify low occurrence mutations from technical noise.  Further, there have been no efficient tools with which such mutations have been able to be detected with sufficient accuracy in single cells, especially neurons.

The method, Mitochondrial DNA Structural Variation Sequencing (MitoSV-seq), is an advance in single-cell sequencing technology that allowed researchers to detect novel mitochondrial DNA mutations, including low occurrence ones, in purified single dopaminergic neurons in a model of Parkinson disease easily while avoiding contamination from non-neurons.

Read full article in EBioMedicine