Researchers at Winship Cancer Institute have developed a technique for detecting an “oncometabolite”, a chemical produced by some brain tumors’ warped metabolism, via non-invasive imaging.
Their approach could allow doctors to know not only that a brain tumor is there, but also that it carries a particular genetic mutation. The researchers’ technique uses magnetic resonance spectroscopy (MRS) to measure a chemical, 2-hydroxyglutarate, which is scarce in normal tissues. 2-hydroxyglutarate is produced by some types of brain tumor carrying mutations in an enzyme called isocitrate dehydrogenase (IDH).
The results were published this week by the Journal of Molecular Medicine.
The research was a collaboration between the laboratories of Hui Mao, PhD, associate professor of radiology and imaging sciences and Emory University Center for Systems Imaging, and Erwin Van Meir, PhD, professor of neurosurgery and hematology and medical oncology. The first author of the paper is postdoctoral fellow Juliya Kalinina. Emory undergraduate Anne Carroll also contributed to the project.
The Emory team is one of several research groups who have obtained similar results recently.
“This is a significant advance, in that we can have a glimpse into the human brain without actually having to do brain surgery,” Van Meir says. “The technique offers the possibility of following up the patient after surgery to see if the treatment is working, by monitoring the decline in levels of the oncometabolite.”
Overview of Brain Cancer
Cancer of the brain can be a primary brain tumor that originates in the brain or a metastatic (secondary) brain tumor that originates from cancer cells that have migrated from other parts of the body.
Primary brain cancer rarely spreads beyond the central nervous system, and death results from uncontrolled tumor growth within the limited space of the skull. Metastatic brain cancer indicates advanced disease and has a poor prognosis.
Primary brain tumors can be cancerous or noncancerous. Both types take up space in the brain and may cause serious symptoms (e.g., vision or hearing loss) and complications (e.g., stroke).
All cancerous brain tumors are life threatening (malignant) because they have an aggressive and invasive nature. A noncancerous primary brain tumor is life threatening when it compromises vital structures (e.g., an artery).
“This technique shows great potential for profiling a brain tumor based on its genetic and metabolic finger-prints,” Mao says. “It may be possible to repeatedly and non-invasively monitor tumor progression, helping physicians to make decisions about the direction and timing of treatment.”
CBTRUS: The incidence rate of all primary malignant and non-malignant brain and central nervous system tumors is 19.9 cases per 100,000 person-years (7.3 per 100,000 person-years for malignant tumors and 12.5 per 100,000 person-years for non-malignant tumors). The rate is higher in females (21.3 per 100,000 person-years) than males (18.3 per 100,000 person-years).
CBTRUS: An estimated 66,290 new cases of primary non-malignant and malignant brain and central nervous system tumors are expected to be diagnosed in the United States in 2012.
SEER: The incidence rate of primary malignant brain and central nervous system tumors (excluding lymphomas, leukemias, tumors of pituitary and pineal glands, and olfactory tumors of the nasal cavity) for the years 2004-2008 is 6.5 cases per 100,000 person-years. This rate is higher in males (7.7 per 100,000 person-years) than females (5.4 per 100,000 person-years).
SEER: The incidence rate of primary non-malignant brain and central nervous system tumors for the years 2004-2008 is 12.8 cases per 100,000 person-years. In contrast to malignant brain and central nervous system tumors, this rate is higher in females (15.3 per 100,000 person-years) than males (10.1 per 100,000 person- years).
ACS: An estimated 22,910 new cases of primary malignant brain and central nervous system tumors are expected to be diagnosed in the United States in 2012 (12,630 in males and 10,280 in females). This represents 1.4% of all primary malignant cancers expected to be diagnosed in the United States in 2012.
IARC: The worldwide incidence rate of primary malignant brain and central nervous system tumors in 2002, age-adjusted using the world standard population, is 3.7 per 100,000 person-years in males and 2.6 per 100,000 person-years in females. This represents an estimated 108,277 males and 81,305 females who were diagnosed with a primary malignant brain tumor in 2002, an overall total of 189,582 individuals. The incidence rates are higher in more developed countries (males: 5.8 per 100,000 person-years; females: 4.1 per 100,000 person-years) than in less developed countries (males: 3.0 per 100,000 person-years; females: 2.1 per 100,000 person-years).
CBTRUS: CBTRUS has calculated a worldwide estimate of 186,678 newly diagnosed primary non-malignant brain and central nervous system tumors per annum for 2002 (males: n=80,759; females: n=105,918).
Mutations in the genes IDH1 or IDH2 cause a distortion of cells’ metabolic cycles and the accumulation of 2-hydroxyglutarate. The presence of the mutations means patients generally survive longer, but they don’t respond as well to standard radiation and chemotherapy treatments.