Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q

Lorena V. Baroni, Lakshmikirupa Sundaresan, Ayala Heled, Hallie Coltin, Kristian W. Pajtler, Tong Lin, Thomas E. Merchant, Roger McLendon, Claudia Faria, Molly Buntine, Christine L. White, Stefan M. Pfister, Mark R. Gilbert, Terri S. Armstrong, Eric Bouffet, Sachin Kumar, Michael D. Taylor, Kenneth D. Aldape, David W. Ellison, Nicholas G. GottardoMarcel Kool, Andrey Korshunov, Jordan R. Hansford, Vijay Ramaswamy

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

44 Citaten (Scopus)


Background: Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification. Methods: Five independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome-wide methylation arrays for chromosomal and clinical variables predictive of survival. Results: Across all cohorts, 663 PF-EPN-A were identified. The most common broad copy number event was 1q gain (18.9%), followed by 6q loss (8.6%), 9p gain (6.5%), and 22q loss (6.8%). Within 1q gain tumors, there was significant enrichment for 6q loss (17.7%), 10q loss (16.9%), and 16q loss (15.3%). The 5-year progression-free survival (PFS) was strikingly worse in those patients with 6q loss, with a 5-year PFS of 50% (95% CI 45%-55%) for balanced tumors, compared with 32% (95% CI 24%-44%) for 1q gain only, 7.3% (95% CI 2.0%-27%) for 6q loss only and 0 for both 1q gain and 6q loss (P = 1.65 × 10-13). After accounting for treatment, 6q loss remained the most significant independent predictor of survival in PF-EPN-A but is not in PF-EPN-B. Distant relapses were more common in 1q gain irrespective of 6q loss. RNA sequencing comparing 6q loss to 6q balanced PF-EPN-A suggests that 6q loss forms a biologically distinct group. Conclusions: We have identified an ultra high-risk PF-EPN-A ependymoma subgroup, which can be reliably ascertained using cytogenetic markers in routine clinical use. A change in treatment paradigm is urgently needed for this particular subset of PF-EPN-A where novel therapies should be prioritized for upfront therapy.

Originele taal-2Engels
Pagina's (van-tot)1360-1370
Aantal pagina's11
Nummer van het tijdschrift8
StatusGepubliceerd - 1 aug. 2021


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