Discovery brings hope in fight against brain cancer
"The discovery of the fusion gene brings hope in the fight against glioblastoma,
because the more we know about the origins of the disease, the better chances
we have of finding a targeted cure", says Matti Annala.
Researchers at TUT and the M.D. Anderson Cancer Center in the USA have identified a fusion gene associated with glioblastoma. The discovery signals a major step forward in the battle against this malignant brain tumour.
Glioblastoma is the most common and the most lethal form of brain cancer. About three years ago, the Computational Systems Biology (CSB) research group at Tampere University of Technology (TUT) launched a project under the supervision of visiting FiDiPro Professor Wei Zhang to explore the underlying causes of glioblastoma.
The researchers studied tissue samples from 40 patients with brain cancer, 20 of them with aggressive glioblastoma. They isolated and sequenced millions of RNA fragments from each tumor sample. Using computational methods, the sequence fragments were assembled together and scoured for insights into the function of brain tumour cells.
"These days DNA sequences are analysed using high-performance computing clusters that generate staggering amounts of data. We sift through the data to find abnormal sequences. We try to identify, for example, chromosomal anomalies that disrupt normal cellular functions. Based on the findings, we formulate hypotheses about the origins of cancer," says Matti Annala, one of the researchers who took part in the project.
Treasure hunter in the genome jungle
Research Matti Annala describes his work as an exciting treasure hunt in the world of cells. Surprisingly, he became drawn to biology research only about three years ago when he joined the Computational Systems Biology group at TUT. He had previously studied signal processing and software engineering and was instantly attracted to the field. The discovery of the fusion gene has fuelled his enthusiasm even further.
"I managed to detect something that may one day prove to be of immense value," he says.
Annala is currently part of the Bioinformatics group made up of researchers from Tampere University of Technology and the University of Tampere. They work in close collaboration with another local group that conducts world-class research on the genetics of prostate cancer.
The race is on to find more fusion genes and so far the results seem promising. The group has recently identified two novel fusion genes in a sequencing study involving a cohort of 41 prostate cancer patients.
"We hope that our efforts contribute to the development of new cancer treatments," says Matti Annala
Chromosomes convey distorted messages
For Matti Annala, the project was a personal triumph. Using an algorithm that he had developed, he detected the fusion of two genes in two of the analysed glioblastoma samples.
"A fusion gene is formed when a chromosome breaks and the pieces are jumbled up. Sometimes pieces from two separate genes are brought together to form a hybrid gene. Such a fusion gene may induce abnormal cell behaviour, such as uncontrolled cell proliferation typically associated with cancer."
Annala's significant discovery prompted researchers at the Cancer Genomics Core Laboratory in Houston to continue the project. The lab is headed by Professor Wei Zhang and located in the M.D. Anderson Cancer Center, one of the leading cancer research and treatment centres in the USA.
Matti Annala joined the Houston-based research group for close to a year. He and Researcher Brittany Parker confirmed that the fusion gene identified during the initial project at TUT contributes to the occurrence and progression of glioblastoma.
Targeted drugs are easier on the patient
"The discovery of the fusion gene brings hope in the fight against glioblastoma, because the more we know about the origins of the disease, the better chances we have of finding a targeted cure", says Matti Annala.
"Targeted drugs have, for example, transformed the outlook for patients with chronic myeloid leukaemia. When the fusion gene that causes this cancer of the blood was identified, researchers were able to develop a drug called imatinib that works for 95 per cent of patients."
The researchers in Houston are currently testing several drugs known to target the genes participating in the fusion gene.
"Unlike cytostatic drugs that also affect healthy cells and cause substantial side effects, targeted molecular therapy is easier on the patient, because the fusion gene is not found in healthy cells."
"Later research has indicated that our fusion gene also contributes to the development of bladder and lung cancer. The best-case scenario is that a drug that targets a fusion gene linked to a specific type of cancer could be used to treat multiple types of cancer," says Annala.
Read more about the study.