Michelle M Hanna, the founder and CEO of Ribomed Biotechnologies, received her PhD in Chemistry from the University of California, Davis and did her Postdoctoral work in Biochemistry and Molecular Genetics as an American Cancer Society Postdoctoral Fellow at the University of California, Berkeley. She was an Assistant Professor of Biological Chemistry at the University of California, Irvine, College of Medicine, where she received Young Investigator awards from the American Cancer Society and the Beckman Foundation, and an Associate Professor of Biochemistry until she founded Ribomed. She is the Inventor of the Abscription/CAPS technology. She has been awarded over $10 million in grants and contracts and her work has resulted in numerous publications and patents. She also serves on the Grant Review Board for
Praespero, an autoimmune disease foundation.
In 2016, the World Health Organization announced new guidelines for the stratification of brain tumors (gliomas) before treatment. In addition to MGMT methylation, molecular biomarkers now recommended include mutations in IDH1 and IDH2 (primarily IDH1 R132H) that cause the glioma CpG island methylator phenotype (G- CIMP). The methylated phenotype correlates with longer survival. Tumor samples received by clinical laboratories often contain insufficient DNA to measure gene-specific
DNA methylation for even a single target with bisulfite or methylation-sensitive restriction enzyme (MSRE) based methods, so it has become practice to infer CIMP from the presence of the IDH1 R132H mutation identified by sequencing. This can cause CIMP to be missed.
To simultaneously measure DNA methylation and associated mutations, even in challenging samples of low concentration or damaged DNA, a new method, coupled abscription PCR signaling (CAPS), was developed. Samples from patients with recurrent high-grade glioma (HGG) were analyzed using CAPS to measure: MGMT promoter methylation; methylation of a three-gene panel for G-CIMP, and; the IDH1 R132H mutation. IDH1 was also sequenced. In 26/26 samples, results for R132H with CAPS matched sequencing. In 25/26, CIMP status from the three-gene methylation panel correlated with the R132H status. In one case, both CAPS and sequencing scored negatively for R132H, but the tumor was clearly CIMP+ based on DNA methylation. Additional sequencing showed this sample contains the IDH1 R132S mutation, which also induces CIMP.
Additionally, some samples were negative for any IDH mutation but were highly methylated, indicating that CIMP was epigenetically imprinted, followed by loss of the mutation. CAPS detection makes it possible to now analyze multiple methylation biomarkers, even with limited FFPE tumor material. This MGMT/CIMP/IDH1 R132H diagnostic (GliomaSTRAT) increases the applicability and reliability for prognostic assessment of patients diagnosed with brain cancer compared to currently available assays and allows CIMP to be determined definitively.