The research of Robert B. Jenkins, M.D., Ph.D., is focused on cancer genetics, particularly elucidation of the genetic events important for cancer initiation and progression. His primary interest is in the genetics of gliomas, where both his basic genetic studies and clinical translation activities have had a major impact on neuro-oncology.
Dr. Jenkins' lab has worked in several areas of neuro-oncology. For example, the lab developed carrier peptides to deliver proteins and small molecules across the blood-brain barrier, technology which has been licensed by several drug companies and is showing evidence of success for the treatment of neurological disorders.
The lab was also involved in the development of the Food and Drug Administration (FDA)-approved dual-probe fluorescence in situ hybridization (FISH) test that is used to stratify patients for the treatment with HER2-targeted therapies.
Dr. Jenkins' team has developed an expression profiling test that predicts which men with prostate cancer are likely to develop clinical progression. This test is nearing submission for FDA approval.
Dr. Jenkins has also been involved in the development of several other genetic tests, including an FDA-approved urine screening test for bladder cancer (for which he holds the patent) as well as multiple FISH and array comparative genomic hybridization tests.
Genetic markers of nervous system tumors (oligodendrogliomas). Dr. Jenkins' research team was the first to discover that deletion of the 19q chromosome arm was observed in approximately 50 percent of oligodendrogliomas. A group in Germany observed 1p deletion at a similar prevalence. Careful mapping studies by Dr. Jenkins' group showed that the 1p and 19q deletions occurred together and that most of the deletions involved the whole 1p and 19q arms.
At that time, Dr. Jenkins' team developed a FISH assay to detect these deletions — a test that became part of the standard of practice for the pathologic diagnosis of oligodendroglioma. The team then used stem cell culture techniques to discover that an unbalanced translocation generates 1p and 19q codeletion.
- Discerning the predictive value of 1p and 19q codeletion in the treatment of high-grade gliomas. With J. Gregory Cairncross, M.D., at the University of Calgary, Dr. Jenkins demonstrated that codeletion of 1p and 19q predicts a significantly better prognosis as well as a better response to procarbazine, lomustine and vincristine (PCV) chemotherapy. Drs. Cairncross and Jenkins also demonstrated that when patients who have grade III gliomas of oligodendroglial lineage with both mutation of the IDH gene and codeletion of 1p and 19q receive PCV chemotherapy and radiation therapy, they have significantly longer survival periods than those who receive only radiation therapy (median 14.7 years vs. 6.8 years, respectively). Collectively, these findings have changed the standard of practice for the care of patients with oligodendroglial tumors.
- Genome-wide association studies (GWASs) of gliomas and fine mapping of the 8q24 locus. With the group of Margaret R. Wrensch, M.P.H., Ph.D., at University of California, San Francisco, Dr. Jenkins performed one of the first two GWASs in glioma. Drs. Jenkins and Wrensch then embarked on a fine-mapping study of the 8q24 (and other) regions, and they completed the first fine-mapping study of a GWAS hit — discovering a variant in 8q24 that confers a significant risk for the development of IDH-mutant gliomas. Nearly 50 percent of patients with IDH mutant gliomas and oligodendroglial tumors carry the risk allele for variance, compared with approximately 5 percent of the general population. Analysis of the fine-mapping data of specific regions is ongoing.
- Germline associations with specific molecular genetic subgroups of glioma. Soon after the discovery of the 8q24 and 11q23 germline associations, Drs. Jenkins and Wrensch determined that these were associated with the development of gliomas that go on to acquire IDH mutation, codeletion of 1p and 19q, or both. Besides IDH mutation and codeletion of 1p and 19q, the promoter of the TERT gene has also been observed to acquire mutations in gliomas. Dr. Jenkins' lab generated a molecular classification of gliomas based on the presence or absence of acquired 1p and 19q, IDH, or TERT alterations. Each of the five groups — triple positive, IDH mutation only, TERT and IDH mutation, TERT only, and triple negative — had a characteristic age of onset, a specific pattern of additional acquired molecular genetic alterations, and among grade II and III gliomas, a different overall survival. In addition, particular germline single-nucleotide polymorphisms were associated with the development of each of the different molecular subtypes of glioma. Dr. Jenkins' team is currently working to understand the biological (functional) relationships between the germline and acquired alterations among some of these different molecular subtypes of glioma.
Significance to patient care
One of Dr. Jenkins' earliest lifetime goals was to direct both a clinical laboratory and a research laboratory. Thus, he is focused on developing new diagnostic and predictive tests for use in for various cancers.
- Advisory board member, National Brain Tumor Society, 2013-present; Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence (SPORE), 2010-present; UCLA Brain Tumor SPORE, 2010-present; Collaborative Ependymoma Research Network, 2010-present
- Co-principal investigator, Mayo Clinic Brain Cancer SPORE, 2004-present
- Ting Tsung and Wei Fong Chao Professor of Individualized Medicine Research, Mayo Clinic, 2012
- The Victor Levin Award and Lecture in Neuro-Oncology Research, Society for NeuroOncology, 2012
- Founding member, Cancer Biomarkers Study Section, National Institutes of Health, 2004-2008