Mbrs-34. Molecular Characterization of Recurrent Medulloblastoma Reveals an Unexpectedly High Incidence of Secondary Malignancy
Year: 2018
Type: conference-abstract
Abstract: Despite an overall 5-year progression free survival of approximately 80% for primary medulloblastomas (MBs), recurrent disease confers an abysmal prognosis with less than 10% 5-year survival. Subgroup affiliation at recurrence has been reported as stable though divergent clonal selection may explain treatment failure upon relapse. The confirmation of histopathologic diagnosis at recurrence thus represents a key task to facilitate selection of efficacious therapy and to gain deeper understanding of the biology driving recurrent disease. DNA methylation-based classification of pediatric brain tumors has emerged as a robust methodology for refining histopathologic diagnosis and defining disease-specific subgroups. We leveraged Illumina Infinium BeadChip arrays to characterize a series of >50 patient-matched, histopathologically diagnosed, primary/relapse MB pairs. Entity and subgroups were assigned by comparison with a database consisting of >2800 reference methylation profiles (https://www.molecularneuropathology.org/mnp). Genome-wide copy-number aberrations were inferred from the BeadChip arrays, and mutational analysis (whole exome sequencing) was performed on the majority of samples. Molecular classification was performed on n=59 primary/relapse MB pairs, inferring the following subgroup representation amongst our cohort: WNT (n=1, 2%), SHH (n=17, 30%), Group 3 (n=15, 25%), Group 4 (n=25, 42%). MB subgroup status was highly conserved across the series (90%), consistent with prior reports. Notably, we determined that 6/59 (10%) of histopathologically diagnosed MB ‘relapses’ molecularly classified as non-MB, including multiple glioblastomas (3/6). Pairwise copy-number and mutational analyses are ongoing to determine the degree of conservation and/or divergence amongst somatic alterations between primary/relapse MB pairs and to identify molecular patterns associated with secondary malignancy.
Source: Neuro-Oncology
Institutions: St. Jude Children's Research Hospital, German Cancer Research Center, National Center for Tumor Diseases, Hopp Children's Cancer Center Heidelberg, Children's Hospital Los Angeles, The University of Texas Southwestern Medical Center, Texas Children's Hospital, Seattle Children's Hospital
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2809428202