Tracking treatment-resistant cells in bowel cancer

Reza Roozitalab Posted in General News, Publications 02 January 2018

A powerful new tool for cancer research

Lead author Dr Ann-Marie Baker and post doctoral research assistant Dr Weini Huang (right)

 Scientists at the BCI have applied a new method to precisely map the location of potentially treatment-resistant mutant cells inside human tumours.

The new method, named BaseScope, allows researchers to see how cells that carry a particular genetic mutation are organised within a tumour.

These ‘maps’ of mutant cancer cells (see picture below) reveal new information about how tumours grow.

The BaseScope tool is very sensitive at detecting mutant cells, and also shows which type of tumour cells (more benign or more aggressive) carry the mutation.

Together this information could aid doctors in determining the most suitable treatment for individual patients.

The findings of the research, published in Nature Communications, describe the application of a series of carefully designed molecular probes that ‘stick’ to RNA in the cancer cells carrying a specific mutation. The probes stick only to the mutant cells, and the tumour is examined under a microscope to reveal which cells contain the genetic mutation of interest (visualised as red dots, see picture above).

Indeed the team found the method to be highly sensitive and specific, allowing them to detect even just a few mutant cells. These tiny populations of mutant cells would have been missed if previously available methods were used.

Using this approach, the team, led by postdoctoral researcher Dr Ann-Marie Baker, and supported by Dr Weini Huang (BCI), Professor Trevor Graham (BCI), Professor Ian Tomlinson (Birmingham) and a team from Advanced Cell Diagnostics (ACD, a technology company from the USA), were able to create detailed 2D maps showing the location of mutant cells within colorectal cancers.

Trevor Graham 2018

Professor Trevor Graham said:

I’ve been tremendously excited about this work: its amazing to see, for the first time, the arrangement of mutant clones inside human tumours. These data represent a new opportunity for us to work out exactly how human cancers change over space and time.

 

Unlike previous methods that involve genetic sequencing of individual cancer cells or large ‘bulk’ pieces of tumour tissue, BaseScope preserves the spatial location of mutant cells, allowing researchers to better understand their behaviour and directly see rare subpopulations as they appear and spread across the tumour.

By combining these data with computational modelling, the team could work out when the new mutant cancer cells arose and how quickly they spread through the cancer.

The team at BCI have implemented BaseScope as a powerful research tool in the laboratory, and the next steps will involve further development to make BaseScope a cost-effective diagnostic tool to direct personalised treatment in the hospital.

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