Finding genetic cancer risks

February 05, 2020

Germline variants are present in every single cell of our body. By contrast, somatic mutations occur in individual body cells during an organism's lifetime and only affect the tissue that is derived from that cell. They can be driven by external factors like UV light or tobacco smoking. "The main finding of our study is that a person's genetic background can influence the changes we see in the genome of their cancer cells," says Sebastian Waszak; a postdoctoral fellow in the Korbel group at the time the research began.

A clock-like mutational process

"Cancer is a disease of the somatic genome, caused by mutations that arise during our lifetime," says EMBL group leader Jan Korbel. "But in a certain number of patients, at least 5 to 10%, the reason for cancer is due to inherited mutations. In our study we identified several genetic factors that promote the somatic evolution of cancer cells."

The group identified germline mutations in the gene MBD4 as a driver for an overabundance of somatic mutations in cancer genomes. MBD4 influences a mutational process that occurs naturally during ageing and is described as clock-like, because of the rhythm with which somatic mutations occur during our lifetime. In the presence of a mutated MBD4 gene, the clock-like mutational process runs at a much faster pace.

Finding germline variants that influence cancer development is key for future medical applications. "Our methodology can be used to identify genetic factors that increase the pace at which somatic mutations are acquired," says Sebastian Waszak. In the future, patients with an identified genetic risk could be counselled and offered regular screenings so that a pre-cancerous lesion is discovered as early as possible.

Organisation and creativity

The working group responsible for this segment of the main Pan-Cancer paper included as many as 100 scientists. "We were very excited to understand the influence of genetic factors on cancer development," says Sebastian Waszak. "This was a project born out of curiosity and everybody contributed lots of resources to it. It was also an organisational challenge." Weekly teleconferences were held from EMBL to coordinate interests and roles, to discuss results, and to organise workshops.

"There are many open questions when it comes to understanding cancer risks," says Sebastian Waszak. "Pan-Cancer has enabled us to study the early steps of cancer development from a novel perspective."

The Pan-Cancer project

The Pan-Cancer Analysis of Whole Genomes project is a collaboration involving more than 1300 scientists and clinicians from 37 countries. It involved analysis of more than 2600 genomes of 38 different tumour types, creating a huge resource of primary cancer genomes. This was the starting point for 16 working groups to study multiple aspects of cancer development, causation, progression, and classification.

European Molecular Biology Laboratory

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 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