CRISPR offers new insights into critical cancer changes

Pancreatic cancer cells. Credit: Anne Weston, Francis Crick Institute

CRISPR offers new insights into critical cancer changes

16 May 2019 - 09:21

Summary 

  • Researchers have used CRISPR technology to show that certain gene fusions are essential for cancer development
  • Although 90% of the gene fusions tested do not appear to play an essential role in cancer, researchers identified a handful that are key for cell cancer survival
  • The results suggest that certain gene fusions could be used to diagnose and guide cancer treatment

May 16, Cambridge – Researchers at the Wellcome Sanger Institute, EMBL-EBI, Open Targets, GSK and collaborators have used CRISPR technology to uncover which gene fusions are critical for the growth of cancer cells. The team also identified a new gene fusion that presents a novel drug target for multiple cancers, including brain and ovarian cancers.

Gene fusions are caused by the abnormal joining of two otherwise different genes. They are currently used as diagnostic tools to predict how particular cancer patients will respond to drugs, as well as prognostics, to estimate the outcome for a patient given the best possible care. Gene fusions are also the targets of several recent cancer treatments.

Essential gene fusions

A paper published in Nature Communications has given more certainty for the use of specific gene fusions to diagnose and guide the treatment of patients. Researchers suggest existing drugs could be repurposed to treat some people with pancreatic, breast and lung cancers, based on the gene fusions found in their tumours.

The researchers analysed more than 8000 gene fusions in over 1000 human cancer cell lines from 43 different cancer types. The team tested the cell lines against more than 350 anti-cancer drugs to see which existing drugs could be repurposed to potentially treat patients with gene fusions, and employed CRISPR as a tool to discover which key gene fusions are critical for cancer cell survival.

The team found that 90 per cent of gene fusions do not play an essential role in cancer, but also identified a handful that are key for cell cancer survival. These results should be considered when inferring causes of cancer from the genome sequence of patients’ tumours.

More targeted clinical studies

“Cancers differ between people and having a genomic view of these differences is increasing our understanding of cancer and opening up treatment options for patients,” says Julio Saez-Rodriguez, previously at EMBL-EBI and Open Targets, and now at Heidelberg University. “This study offers further opportunities to employ gene fusions as therapeutic biomarkers and stratify patients onto clinical trials, potentially offering more targeted and effective clinical studies.”

Researchers also discovered a new fusion, YAP1-MAML2, which is essential for the progression of multiple cancer types, such as brain and ovarian cancers.

This research, led by Gabriele Picco from the Wellcome Sanger Institute, and coordinated by Matthew Garnett from the Wellcome Sanger Institute and Open Targets, contributes towards building the Cancer Dependency Map, a rulebook for the precision treatment of cancer in the future.

Read the full press release on the Wellcome Sanger Institute website

Source articles

PICCO, G., et al. (2019). Functional linkage of gene fusions to cancer cell fitness assessed by pharmacological and CRISPR-Cas9 screening. Nature Communications. Published online 16 05; DOI: 10.1038/s41467-019-09940-1

Contact the news team

Oana Stroe
Communications Officer
stroe@ebi.ac.uk
+44 (0)1223 494 369

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