Rarity of PTEN deletions and EGFR amplification in malignant gliomas of childhood: results from the Children's Cancer Group 945 cohort

Abstract

Object: In reporting on molecular studies involving malignant gliomas in adults, authors have noted that deletions of PTEN and amplification of EGFR are common and may contribute to tumor development, providing a rationale for a number of therapies aimed at these molecular targets. The frequency of comparable abnormalities has not been defined in a sizable pediatric cohort. To address this issue, we examined tumor samples from the Children's Cancer Group 945 study, a large randomized trial of treatment for childhood malignant gliomas.

Methods: Tissue sections in 62 evaluable cases were examined, and the tumors were isolated by microdissection. Polymerase chain reaction amplification was used to detect PTEN mutations. Deletions of PTEN were also assessed by fluorescence in situ hybridization (FISH) in 27 cases and loss of heterozygosity analysis in 54; EGFR was assessed using immunohistochemistry to identify areas with maximal EGFR expression, followed by FISH to determine EGFR amplification. Alteration of the PTEN sequence was detected in just one of 62 tumors, in conjunction with loss of chromosome 10; PTEN deletions without mutation were evident in seven additional tumors. The PTEN alterations were more common in glioblastoma multiforme (seven of 25 tumors) than other tumor subgroups (one of 37 tumors) (p = 0.0056). Although 14 of 38 evaluable tumors had increased EGFR expression compared to normal tissue, only one tumor exhibited amplification of EGFR.

Conclusions: Alterations in PTEN and amplification of EGFR are uncommon in pediatric malignant gliomas, in contrast to adult malignant gliomas. From this one can infer that the pediatric and adult tumors involve distinct molecular causes. The results of this study have important implications for the adaptation of glioma therapies aimed at molecular targets in adults to the treatment of childhood gliomas, and highlight the need for investigations of therapies specifically directed toward childhood tumors.