Mutations driving leukemia identified

October 15, 2015

Johannes Reiter, former PhD student in the group of Krishnendu Chatterjee at the Institute of Science and Technology Austria (IST Austria), is co-author of a Nature paper on genetic alterations that drive the progression and relapse of cancer. An international team of scientists from the US, Germany and Austria identified novel genes associated with chronic lymphocytic leukemia through the analysis of high-throughput sequencing data.

Knowing the genetic alterations that provide a selective advantage to the cancer cells is essential for understanding the evolution of cancer and provides the foundation for new therapies. The team of scientists analyzed sequencing data of all protein-coding genes in a genome (called whole-exome sequencing) from 538 chronic lymphocytic leukemia (CLL) patients. CLL is the most common type of leukemia and occurs mostly in adults.

Utilizing sophisticated data analysis methods, the scientists identified 44 genes that are frequently mutated in CLL patients. These mutations are so-called "driver mutations": while cancer cells (as well as normal cells) accumulate many mutations as they age, the driver mutations are those that actually cause the cancer to arise or grow;, while passenger mutations have no functional consequences for cancer growth. 18 of these 44 driver mutations have previously been identified, while the remaining 26 are additional putative CLL driver genes potentially affecting cancer progression. Moreover, the researchers found 11 somatic copy number variations that were present more often than expected by chance. The identified driver genes affect RNA processing and export, the activity of MYC, a transcription factor that plays a role in apoptosis, and MAPK signaling, a signaling pathway implicated in many forms of cancer.

In addition, the authors uncovered genetic features that contribute to a relapse of the disease. The large number of analyzed samples also enabled them to infer which driver mutations arise early and which arise late. They could so study the typical temporal sequence of cancer progression and explore evolutionary relationships among driver genes. Mutations that affect the clinical outcome of the disease were also identified. In particular TP53, SF3B1 and RPS15 mutations were associated with shorter progression-free survival of patients.

This study shows that large sequencing data sets enable the discovery of novel genes associated with cancer as well as the impact of driver gene mutations on relapse and clinical outcome.
-end-


Institute of Science and Technology Austria

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.