In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. LB-82-LB-82
Abstract:
In contrast to histopathological grading which varied in respect to its prognostic value between different clinical trials, extent of resection was found to be consistently associated to the clinical outcome. In retrospective series, gain of genetic material of chromosome arm 1q was identified to predict worse outcome. This marker was mainly assessed by FISH analysis which typically showed failure rates of 15-20 % in archival material. To validate this marker in a homogenously treated patient cohort, we analysed chromosome 1qin 209 consecutive cases enrolled into the multicenter trial HIT2000 (postoperative chemotherapy and irradiation, in a sequence depending on age and extent of resection) in which formalin-fixed, paraffin embedded material was available for DNA extraction. By using multiplex ligation-dependent probe amplification (MLPA) for 5 markers located on chromosome 1q and control markers, we were able to analyse 206/209 samples ( & gt; 98 %) and found a gain of chromosome 1q in 35 cases (17 %). 135/206 ependymomas were located in the infratentorial region. 35 cases were diagnosed as WHO grade II ependymoma, 171 as anaplastic ependymoma (WHO grade III). Interestingly, only 2 of the 35 WHO grade II ependymomas had 1q gain (5.7%). At a median follow-up of 3.9 years for survivors, patients with tumors showing 1q gain had a significantly lower 4-year overall survival (OS) (±SE) of 58% +/- 9% compared to patients lacking this marker (89% +/- 3%, p=0.002). The distribution of this marker was similar when comparing patients with supra- and infratentorial tumors. Multivariable analysis demonstrated that residual tumor and infratentorial localization were independent risk factors for event-free survival, and gain of chromosome 1q for OS, respectively. In conclusion, we validated chromosomal 1q gain to be a useful independent genetic marker for risk stratification of pediatric ependymoma patients which can be evaluated by MLPA representing a robust, reliable and cost-efficient method. Citation Format: Torsten Pietsch, Evelyn Doerner, Anja zur Muehlen, Natalia Velez-Char, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Katja von Hoff, Carsten Friedrich, Stefan Rutkowski, Andre O. von Bueren. Chromosome 1q gain as genetic marker for risk stratification of pediatric ependymoma patients - validation as an adverse prognostic marker in the German multicenter HIT2000 trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-82. doi:10.1158/1538-7445.AM2013-LB-82
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-LB-82
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
