Study reveals every bowel tumor and bowel cancer cell have unique genetic fingerprints

April 11, 2018

New research on bowel cancer has shown that every tumour is different, and that every cell within the tumour is also genetically unique. In the first study of its kind, researchers from the Wellcome Sanger Institute, UK and Hubrecht Institute (KNAW) in Utrecht, The Netherlands, used the latest single cell and organoid technologies to understand the mutational processes of the disease.

Reported in Nature, the study will help researchers understand mutational processes, and may allow them to target cancer-specific processes for prevention or treatment.

The team worked on tissue from three patients with colorectal cancer, taking normal bowel stem cells and cells from four different areas of the tumours. They then grew these into organoids - 3D 'mini-guts' - in the laboratory to amplify the single cells so they could be studied.

Colorectal cancer is the third most common type of cancer worldwide making up about 10 per cent of all cancer cases, in the UK alone, over 41 thousand people are diagnosed with the disease every year*.

It was known that colorectal tumours contain subclones that react differently to treatment; however, until now it has not been possible to study single cells from tumours and normal tissue to get an accurate picture.

Prof Hans Clevers, from Hubrecht Institute in the Netherlands, joint corresponding author on the paper, said: "Organoids had not been used to study single cancer cells before. Nobuo Sasaki in my lab isolated multiple single cells from the tumors and grew them up as organoids. This enabled us to study each cell without the errors that standard single cell methods bring. For the first time ever, we could make a really comprehensive comparison of individual normal and tumour cells from the exact same type of tissue, taken at the same time, from the same person, and see how the cancer had developed."

The researchers discovered that the tumour cells had many more mutations than normal cells, and that not only was each bowel cancer genetically different, but each cell they had studied within that cancer was different.

Dr Sophie Roerink, joint first author from the Wellcome Sanger Institute, said: "We found mutational processes in these cancer cells that are just not seen in normal cells, leading to a huge increase in mutation rate for tumours compared with normal cells. This then leads to remarkable genetic diversity within the tumours. We knew before that cancers contained subclones, but this is the first time that anyone has shown that each cell in a tumour is different."

The study discovered that the mutational processes in cancer cells are very different from those in healthy cells and that the increase in mutation rate seems to be a general feature of these colon cancers. Their study also suggests that the mutation rate starts to change many years before the cancer is diagnosed. This time window could provide diagnostic clues in the future if it were possible to identify the rise in mutation rate early in a cell.

Prof Sir Mike Stratton, joint corresponding author on the paper from the Wellcome Sanger Institute, said: "This study gives us fundamental knowledge on the way cancers arise. By studying the patterns of mutations from individual healthy and tumour cells, we can learn what mutational processes have occurred, and then look to see what has caused them. Extending our knowledge on the origin of these processes could help us discover new risk factors to reduce the incidence of cancer, and could also put us in a better position to create drugs to target cancer-specific mutational processes directly."
-end-
Notes to editors:

*CRUK figures. http://www.cancerresearchuk.org/about-cancer/bowel-cancer/about-bowel-cancer

Funding: This work was supported by funding from the Wellcome trust (098051), Stichting Vrienden van het Hubrecht and KWF (SU2C-AACR-DT1213 and HUBR KWF 2014-6917).

Selected websites:

About the Hubrecht Institute

The Hubrecht Institute is a research institute focused on developmental and stem cell biology. It encompasses 20 research groups that perform fundamental and multidisciplinary research, both in healthy systems and disease models. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on the Utrecht Science Park 'De Uithof'. Since 2008, the institute is affiliated with the University Medical Center Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit http://www.hubrecht.eu.

About the Royal Netherlands Academy of Arts and Sciences (KNAW)

The Royal Netherlands Academy of Arts and Sciences is the forum, conscience, and voice of the arts and sciences in the Netherlands. It promotes quality in science and scholarship and strives to ensure that Dutch scholars and scientists contribute to cultural, social and economic progress. As a research organisation, the Academy is responsible for a group of fifteen outstanding national research institutes.

Oncode Institute

Oncode Institute is an independent institute whose goal is to translate fundamental insights about cancer to improved and more affordable care for patients as efficiently as possible. A team of renowned cancer researchers working in The Netherlands has joined forces within a mission-driven institute focusing on three pillars: excellent research, intensive collaboration and powerful valorization. The Dutch Cancer Foundation invests, together with the Dutch ministry of Economic Affairs & Climate Policy, the ministry of Education Culture & Science, the ministry of Health, Welfare & Sport, Health~Holland, NWO and ZonMw, a total of €120 million in Oncode Institute until 2022. http://www.oncode.nl/

The Wellcome Sanger Institute

The Wellcome Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. To celebrate its 25th year in 2018, the Institute is sequencing 25 new genomes of species in the UK. Find out more at http://www.sanger.ac.uk or follow @sangerinstitute

Wellcome

Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.wellcome.ac.uk

Wellcome Trust Sanger Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.