Use of a patient-derived cell-line (A1ATD) in research
Research type
Research Study
Full title
Use of a patient-derived cell-line (A1ATD) in research on genes involved in cancer
IRAS ID
262117
Contact name
Mike Stratton
Contact email
Sponsor organisation
Wellcome Sanger Institute
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
We know that after exposing cells to a chemical mutagen in vitro, each cell will acquire mutations that will be passed onto its daughter cells. However the frequency of any given mutation in the population of cells will be too low to detect with standard DNA sequencing against a background of errors introduced at multiple stages of sample processing and analysis. To overcome this problem, it is possible to sequence single-cell derived colonies. However, this method is costly and time consuming. Instead, we can apply ‘duplex sequencing’, which allows specific detection of somatic variants that are found in only one cell. It is the duplex sequencing method which we wish to test the proof of concept in the current studies.
We wish to use an induced pluripotent stem cell line (iPSC - a cultured, immortalised cell line) known as A1ATD in order to carry out a proof of concept experiment for a new duplex sequencing method. This cell line has been previously used at the Sanger Institute to look at the effects of chemical exposures (REC approval 14/NW/1029). In the previous study the researchers exposed the cell line to particular chemicals and then sequenced its DNA, they were able to show that particular patterns of DNA mutations (known as ‘mutational signatures’) resulted from exposure to a particular chemical. The chemically-treated A1ATD cell line was stored and we now wish to use this treated cell line to test a new duplex sequencing method, and compare our data back to the standard sequencing technique used previously to see if we can still detect the mutational signatures.
REC name
East of Scotland Research Ethics Service REC 2
REC reference
19/ES/0037
Date of REC Opinion
26 Mar 2019
REC opinion
Favourable Opinion