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Molecular classification of medulloblastomas(MB) is prognostically and therapeutically relevant and helps in better risk-stratification. Translation of this subgrouping to routine practice still remains a challenge. The most pathologist-accessible techniques for molecular subgrouping include immunohistochemistry(IHC), fluorescent in-situ hybridization(FISH) and Nanostring assay. Objectives:(1)Molecular subgrouping of MBs by IHC and FISH, and Nanostring Assay (2)To compare their efficacy against sequencing and DNA methylation, and cost for applicability in resource-constrained centers METHODS Ninety-five cases of MB with adequate tissue were included. Molecular subgrouping was performed by IHC for β-catenin, GAB1, YAP1, and p53; FISH for MYC amplification, and sequencing for CTNNB1, and by Nanostring Assay on the same set of MBs. Further, a subset of cases were subjected to 850k DNA methylation array. RESULTS IHC+FISH classified MBs into 15.8% WNT, 16.8% SHH, and 67.4% non-WNT/non-SHH subgroups; with MYC amplification identified in 20.3% cases of non-WNT/non-SHH. A single showed diffuse strong p53 positivity among the SHH subgroup. Nanostring successfully classified 91.5% MBs into 25.3% WNT, 17.2% SHH, 23% Group3 and 34.5% Group4. However, Nanostring assay failure was seen in eight cases, all of which were &gt;8-years-old formalin-fixed paraffin-embedded tissue blocks. Concordant subgroup assignment was noted in 88.5% cases, while subgroup switching was seen in 11.5% cases. Both methods showed prognostic correlation. Among the 5 discrepant cases, which switched to WNT subgroup by Nanostring, only 2 were found to have CTNNB1 mutation. Methylation profiling performed on discordant cases revealed 1 out of 4 extra WNT identified by Nanostring to be WNT, others aligned with IHC subgroups; extra SHH by Nanostring turned out to be SHH by methylation. CONCLUSIONS Both IHC supplemented by FISH and Nanostring are robust methods for molecular subgrouping, albeit with few disadvantages. IHC cannot differentiate between Groups 3 and 4, while Nanostring cannot classify older-archived tumors, and is not available at most centres. WNT subgroup with the best prognosis is best detected by IHC or IHC followed by sequencing for confirmation. Nanostring Assay is better suitable to separate Group 3, the worst prognostic group from Group 4. Thus, both the methods complement each other and can be used in concert for high confidence allotment of molecular subgroups in clinical practice. The cost of IHC plus Nanostring will almost be the same as IHC plus FISH. We recommend a cost-efficient algorithmic approach using histopathological subtype and IHC as the first step followed by Nanostring or FISH, wherever suitable.

P14.117 Cost efficient test algorithm for molecular subgrouping of medulloblastomas for day-to-day practice in resource limited countries