Skip to main content
An official website of the United States government
Grant Details

Grant Number: 5R01CA222146-06 Interpret this number
Primary Investigator: Poisson, Laila
Organization: Henry Ford Health System
Project Title: Molecular and Clinical Evaluation of the Glioma Patient Experience to Anticipate Modern Outcomes and Guide Patient Care
Fiscal Year: 2023


Project Summary Landmark papers published recently by us, and others, mark the new era of molecular diagnoses and precision therapy for glioma. In the summer of 2016, the World Health Organization (WHO) published updated diagnosis criteria for glioma that include molecular markers, taking a first step toward a molecularly precise diagnosis. It is our long-term goal to capitalize on the longitudinal resources of brain tumor banks to rapidly assess molecular hypotheses for prognosis and treatment of glioma. With the significant contribution of 240 cases from Henry Ford Hospital (HFH), an effort to molecularly and clinically profile glioma was started by The Cancer Genome Atlas (TCGA) project. Capitalizing on our clinically annotated brain tumor bank at HFH, we will focus on therapeutic outcomes, recurrent disease, and extended survival, which were not captured in the TCGA project. For this work, we have constructed an interdisciplinary team of collaborators, with clinical and informatics expertise, to profile an additional 340 glioma cases (WHO grade II-IV). In total, we will assess 700 tumor specimens (FFPE/frozen) from the HFH tumor bank (2001-present), representing both primary and matched progressive disease (Aim 1). Molecular data will be generated by exome sequencing to assess DNA sequence and copy number variants, targeted Sanger sequencing to profile the TERT promoter, and DNA methylation array assays to profile the methylome. Clinical annotation from our tumor bank, including long-term follow-up and therapy regimens, will be added to each of the 550 profiled glioma cases. The resulting comprehensively-annotated tumor bank will be an invaluable resource for queries of clinical-molecular associations and the progression of disease, made available to researchers at HFH and beyond. In this proposal we use our database to address two analytical aims: (Aim 2) to carefully design statistical models of prognosis and therapy response among modern diagnosis classes using retrospective records; (Aim 3) to identify genomic differences, per patient, arising over the course of treatment and progression, which we expect will impact therapy decisions and inform standard treatments strategies. As part of the third aim, we will also explore the genomic patterns and clinical response of patients with exceptional survival, which may indicate differential molecular diagnosis or suggest therapeutic avenues for extending survival in others.


The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen.
Authors: Malta T.M. , Sabedot T.S. , Morosini N.S. , Datta I. , Garofano L. , Vallentgoed W. , Varn F.S. , Aldape K. , D'Angelo F. , Bakas S. , et al. .
Source: Cancer research, 2024-03-04; 84(5), p. 741-756.
PMID: 38117484
Related Citations

Glioma progression is shaped by genetic evolution and microenvironment interactions.
Authors: Varn F.S. , Johnson K.C. , Martinek J. , Huse J.T. , Nasrallah M.P. , Wesseling P. , Cooper L.A.D. , Malta T.M. , Wade T.E. , Sabedot T.S. , et al. .
Source: Cell, 2022-06-09; 185(12), p. 2184-2199.e16.
EPub date: 2022-05-31.
PMID: 35649412
Related Citations

A serum-based DNA methylation assay provides accurate detection of glioma.
Authors: Sabedot T.S. , Malta T.M. , Snyder J. , Nelson K. , Wells M. , deCarvalho A.C. , Mukherjee A. , Chitale D.A. , Mosella M.S. , Sokolov A. , et al. .
Source: Neuro-oncology, 2021-09-01; 23(9), p. 1494-1508.
PMID: 33560371
Related Citations

DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features.
Authors: Mosella M.S. , Sabedot T.S. , Silva T.C. , Malta T.M. , Dezem F.S. , Asmaro K.P. , Wells M. , Mukherjee A. , Poisson L.M. , Snyder J. , et al. .
Source: Neuro-oncology, 2021-08-02; 23(8), p. 1292-1303.
PMID: 33631002
Related Citations

Expression and regulatory roles of lncRNAs in G-CIMP-low vs G-CIMP-high Glioma: an in-silico analysis.
Authors: Datta I. , Noushmehr H. , Brodie C. , Poisson L.M. .
Source: Journal of translational medicine, 2021-04-29; 19(1), p. 182.
EPub date: 2021-04-29.
PMID: 33926464
Related Citations

iGLASS: imaging integration into the Glioma Longitudinal Analysis Consortium.
Authors: Bakas S. , Ormond D.R. , Alfaro-Munoz K.D. , Smits M. , Cooper L.A.D. , Verhaak R. , Poisson L.M. .
Source: Neuro-oncology, 2020-10-14; 22(10), p. 1545-1546.
PMID: 32644158
Related Citations

Prognostic Value of Preoperative MRI Metrics for Diffuse Lower-Grade Glioma Molecular Subtypes.
Authors: Darvishi P. , Batchala P.P. , Patrie J.T. , Poisson L.M. , Lopes M.B. , Jain R. , Fadul C.E. , Schiff D. , Patel S.H. .
Source: AJNR. American journal of neuroradiology, 2020 May; 41(5), p. 815-821.
EPub date: 2020-04-23.
PMID: 32327434
Related Citations

Developing Real-world Evidence-Ready Datasets: Time for Clinician Engagement.
Authors: Snyder J.M. , Pawloski J.A. , Poisson L.M. .
Source: Current oncology reports, 2020-04-16; 22(5), p. 45.
EPub date: 2020-04-16.
PMID: 32297007
Related Citations

Longitudinal molecular trajectories of diffuse glioma in adults.
Authors: Barthel F.P. , Johnson K.C. , Varn F.S. , Moskalik A.D. , Tanner G. , Kocakavuk E. , Anderson K.J. , Abiola O. , Aldape K. , Alfaro K.D. , et al. .
Source: Nature, 2019 Dec; 576(7785), p. 112-120.
EPub date: 2019-11-20.
PMID: 31748746
Related Citations

Identification of subsets of IDH-mutant glioblastomas with distinct epigenetic and copy number alterations and stratified clinical risks.
Authors: Li K.K. , Shi Z.F. , Malta T.M. , Chan A.K. , Cheng S. , Kwan J.S.H. , Yang R.R. , Poon W.S. , Mao Y. , Noushmehr H. , et al. .
Source: Neuro-oncology advances, 2019 May-Dec; 1(1), p. vdz015.
EPub date: 2019-07-17.
PMID: 31667475
Related Citations

Clinical and research applications of a brain tumor tissue bank in the age of precision medicine.
Authors: Snyder J. , Poisson L.M. , Noushmehr H. , Castro A.V. , deCarvalho A.C. , Robin A. , Mukherjee A. , Lee I. , Walbert T. .
Source: Personalized medicine, 2019 Mar; 16(2), p. 145-156.
EPub date: 2019-02-28.
PMID: 30816054
Related Citations

Back to Top