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Cytogenetic biomarkers improved medulloblastoma prognostication
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Cytogenetic biomarkers accurately identified high-risk and low-risk patients with medulloblastoma, and a model that combined subgroup with cytogenetic and clinical biomarkers improved overall prognostication, according to study results.
Patients with medulloblastoma are divided into four subgroups — WNT, sonic hedgehog (SHH), Group 3 and Group 4 — according to age, metastatic stage, extent of resection and histologic variant. However, patients may be further classified according to subgroup-specific molecular biomarkers, according to study background information provided by the researchers.
The analysis included 673 patients in the discovery cohort and 453 patients in the validation cohort.
Analyses of clinical variables indicated M2 and M3 macroscopic metastases were associated with poor survival among patients with SHH, Group 3 and Group 4 medulloblastoma. Overall, results showed subgroup and metastatic status combined most accurately predicted prognosis among all patients.
Researchers then analyzed six fluorescence in situ hybridization (FISH) biomarkers — GLI2, MYC, chromosome 11, chromosome 14, 17p and 17q — which they determined were subgroup driven or specific.
Among patients with SHH tumors, GLI2 amplification and 14q loss indicated high- and standard-risk disease, whereas absence of these markers was indicative of low-risk disease.
Among patients with Group 3 tumors, isochromosome 17q and MYC amplification were prognostic markers for poor survival. Chromosome 8q loss and chromosome 1q gain were associated with good prognosis.
Loss of chromosome 11 or gain of chromosome 17 besides 10p loss indicated good prognosis among patients with Group 4 tumors. However, MYCN gain or loss and isochromosome 17q were not associated with survival.
“Because both subgrouping assays and prognostic FISH markers will need to be performed in a Clinical Laboratory Improvement Amendments-approved laboratory, we suggest that these assays be adopted and optimized in most major neuro-oncology centers, whereas smaller centers may consider sending tissues for analysis at larger centers,” the researchers wrote. “Our findings demonstrate the utility of incorporating tumor biology into clinical decision making and offer a novel perspective on risk stratification using FISH applicable on paraffin sections; thus, they could be translated immediately into clinical practice.”
Disclosure: The researchers report no relevant financial disclosures.
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