Abstract:
Introduction: In the last years, DNA methylation array
emerged as a new tool for CNS tumor diagnosis.
Objectives: To analyze the value of methylation assay for
routine CNS tumor diagnosis.
Patients and Methods: We performed methylation
array in 182 CNS tumors (100 gliomas (GL), 27 medulloblastomas
(MDB), 20 ependymomas (EP), 17 neuronal/
glioneuronal tumors (N/GNT), 5 meningiomas,
7 embryonal tumors (ET), and 6 sarcomas) from 2019
for subtyping GL, EP, MDB, meningiomas, and sarcomas,
defining the diagnosis in cases without precise
histological features or confirming the histological
diagnosis.
Results: Scores were >0.75 in 147 cases (81%). The histological
diagnosis was maintained and allowed subtyping
in 127 cases (70%) (77 GL, 27 MDB, 12 EP, etc.),
defined differential diagnoses in 16 cases (9%) (3 sarcomas,
5 ET, 3 EP, etc.), and changed the diagnosis in
4 cases (2%). Scores were ≤0.75 in 35 cases (19%),
however, in 7/14 adult diffuse GL, CNV analysis
(EGFR amplification, and Chr.10q and CDKN2A/B
deletions) led to the diagnosis of the cases as IDH-wt
glioblastomas based on the WHO classification. In
8/35 cases displaying scores ≤0.75, RNA and/or DNA
sequencing was performed and led to the diagnosis of
4 tumors (1 sarcoma, 2 DMG H3K27-altered, and
1 pilocytic astrocytoma). Thus, in 24 cases (13%) diagnosis
could not be achieved; among these cases, 10 were
N/GNT.
Conclusion: The methylation array is a valuable tool to
diagnose most CNS tumors because a single technique
offers both the diagnosis and molecular data, mainly for
adult diffuse GL, MDB, and EP. Nowadays, the main
limitations of the method are the high amount of DNA
necessary for performing the study, economic issues for
developing countries, and the absence in the classifier of
uncommon tumors, such as low-grade N/GNT, and some
of the new tumors of the 2021 WHO classification. The
growth of the case base will improve the identification
skills of the system, probably perfecting its diagnostic
capabilities.
