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. 2019 Sep 6;21(9):1164-1174.
doi: 10.1093/neuonc/noz098.

Polysomy is associated with poor outcome in 1p/19q codeleted oligodendroglial tumors

Hui Chen  1 , Cheddhi Thomas  2 , Felipe Andres Munoz  3 , Sanda Alexandrescu  4 , Craig M Horbinski  5 , Adriana Olar  6 , Declan McGuone  6 , Sandra Camelo-Piragua  7 , Lu Wang  1 , Elena Pentsova  8 , Joanna Phillips  9 , Kenneth Aldape  6 , Wen Chen  8 , A John Iafrate  10 , Andrew S Chi  11 , David Zagzag  12 , John G Golfinos  12 , Dimitris G Placantonakis  12   13 , Marc Rosenblum  1 , Pamela Ohman-Strickland  3 , Meera Hameed  1 , Matija Snuderl  2
Affiliations

Polysomy is associated with poor outcome in 1p/19q codeleted oligodendroglial tumors

Hui Chen et al. Neuro Oncol. .

Abstract

Background: Chromosomal instability is associated with earlier progression in isocitrate dehydrogenase (IDH)-mutated astrocytomas. Here we evaluated the prognostic significance of polysomy in gliomas tested for 1p/19q status.

Methods: We analyzed 412 histologic oligodendroglial tumors with use of 1p/19q testing at 8 institutions from 1996 to 2013; fluorescence in situ hybridization (FISH) for 1p/19q was performed. Polysomy was defined as more than two 1q and 19p signals in cells. Tumors were divided into groups on the basis of their 1p/19q status and polysomy and were compared for progression-free survival (PFS) and overall survival (OS).

Results: In our cohort, 333 tumors (81%) had 1p/19q loss; of these, 195 (59%) had concurrent polysomy and 138 (41%) lacked polysomy, 79 (19%) had 1p/19q maintenance; of these, 30 (38%) had concurrent polysomy and 49 (62%) lacked polysomy. In agreement with prior studies, the group with 1p/19q loss had significantly better PFS and OS than did the group with 1p/19q maintenance (P < 0.0001 each). Patients with 1p/19q loss and polysomy showed significantly shorter PFS survival than patients with 1p/19q codeletion only (P < 0.0001), but longer PFS and OS than patients with 1p/19q maintenance (P < 0.01 and P < 0.0001). There was no difference in survival between tumors with >30% polysomic cells and those with <30% polysomic cells. Polysomy had no prognostic significance on PFS or OS in patients with 1p/19q maintenance.

Conclusions: The presence of polysomy in oligodendroglial tumors with codeletion of 1p/19q predicts early recurrence and short survival in patients with 1p/19q codeleted tumors.

Keywords: 1p/19q codeletion; glioma; oligodendroglioma; polysomy.

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Figures

Fig. 1
Fig. 1
Representative FISH images illustrate the presence and absence of polysomy. (A) 1p and 19q loss without polysomy, (B) 1p and 19q relative loss with concurrent polysomy, (C) 1p and 19q maintenance without polysomy, and (D) 1p and 19q maintenance with polysomy. Red probe is for 1p or 19q; green probe is for 1q or 19p.
Fig. 2
Fig. 2
Clinical outcomes from the presence and absence of polysomy in all patients with 1p/19q codeleted oligodendroglial tumors (A and B) and in a subset of patients with molecularly defined oligodendroglioma, IDH mutant and 1p/19q codeleted (C and D). (A) Kaplan–Meier estimate shows that tumors with 1p/19q loss and polysomy had worse PFS than did tumors with 1p/19q loss and no polysomy (P < 0.0001) and better PFS than did tumors with 1p/19q maintenance (P < 0.01). (B) Tumors with 1p/19q loss and polysomy had better OS than did tumors with 1p/19q maintenance (P < 0.0001) and a trend for worse OS than tumors with 1p/19q loss and no polysomy (P = 0.07). (C) Kaplan–Meier estimate shows that oligodendroglioma, IDH mutant and 1p/19q codeleted with polysomy has worse PFS than did tumors with 1p/19q loss and no polysomy (P < 0.01) and better PFS than did tumors with 1p/19q maintenance (P < 0.05). (D) Oligodendroglioma, IDH mutant and 1p/19q codeleted with polysomy showed a trend for worse OS compared with IDH mutated tumors with 1p/19q loss without polysomy (P = 0.06). *P < 0.05, **P < 0.01, ***P < 0.0001.
Fig. 3
Fig. 3
The presence of polysomy in glial tumors with 1p/19q maintenance did not affect PFS (A, P = 0.36 by log-rank test) or OS (B, P = 0.75 by log- rank test) via Kaplan–Meier estimate. The extent of polysomy with either >30% or <30% polysomy in oligodendroglial tumors with 1p/19q loss did not affect PFS (C, P = 0.76 by log-rank test) or OS (D, P = 0.32 by log-rank test). N.S. = P-value is not significant.
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