Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

Abstract

Aims: Atypical (World Health Organization grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array comparative genomic hybridization to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumours show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample.

Methods: Eighty-six completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow-up was obtained. Utilizing a dual-colour interphase fluorescence in situ hybridization assay, 1q gain was assessed using Bacterial Artificial Chromosome probes directed against 1q25.1 and 1q32.1.

Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas.

Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

Figure 1

Representative examples of 1q32.1 gain by FISH on interphase nuclei. Note two green signals from probes to chromosome 13q12, but three red signals from probes to 1q32.1 [red signal = BAC probe RP11-203F10 (chromosome 1q32.1); green signal = BAC probe RP11-496o2 (chromosome 13q12)].

Figure 2

Atypical meningiomas occurring at age > 55years (A) and atypical meningiomas showing gain at 1q32.1 (B) have worse progression-free survival than those occurring in younger patients or those that do not show gain at 1q32.1 respectively. On multivariate analysis, additional information about 1q32.1 status separates the survival curves beyond separation due to age alone (C). The combination of 1q32.1 gain<1.2 and age<55 appears to be associated with improved predicted survival of 10–20% at each time point relative to that associated with age<55 alone.

Figure 2

Atypical meningiomas occurring at age > 55years (A) and atypical meningiomas showing gain at 1q32.1 (B) have worse progression-free survival than those occurring in younger patients or those that do not show gain at 1q32.1 respectively. On multivariate analysis, additional information about 1q32.1 status separates the survival curves beyond separation due to age alone (C). The combination of 1q32.1 gain<1.2 and age<55 appears to be associated with improved predicted survival of 10–20% at each time point relative to that associated with age<55 alone.

Figure 2

Atypical meningiomas occurring at age > 55years (A) and atypical meningiomas showing gain at 1q32.1 (B) have worse progression-free survival than those occurring in younger patients or those that do not show gain at 1q32.1 respectively. On multivariate analysis, additional information about 1q32.1 status separates the survival curves beyond separation due to age alone (C). The combination of 1q32.1 gain<1.2 and age<55 appears to be associated with improved predicted survival of 10–20% at each time point relative to that associated with age<55 alone.