These results suggest that a gene or genes in addition to TP53 on 17p may be involved in the etiology or progression of high-grade astrocytomas and aggressive JPAs in children.(ABSTRACT TRUNCATED AT 250 WORDS)
Telomeric chromosome arm 17p markers 144-D6 and ABR were lost in 6 (75%) of 8 informative tumors classified as high-grade (7 AAs, 1 GM) and in 2 (10%) of 20 informative JPAs.
In fact, the highest percentage of bcl-2 immunoreactive cells was noted in low-grade gliomas, that is, in juvenile pilocytic astrocytomas and oligoastrocytomas.
We studied 75 astrocytic tumors with different degrees of anaplasia including juvenile pilocytic astrocytoma (JPA), low-grade astrocytoma (LGA), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM) to determine whether standard CD44 (CD44s) can be used as a clinically useful marker distinguishing between low- and high-grade gliomas.
Unusual findings include: TP53 mutation in a juvenile pilocytic astrocytoma; TP53 and PTEN mutations in a de novo glioblastoma, a gliosarcoma with identical mutations in gliomatous and sarcomatous components, and an infratentorial anaplastic astrocytoma with an earlier supratentorial grade II astrocytoma bearing the same TP53 mutation but not the PTEN mutation or loss of heterozygosity (LOH) of 10q23.
Unusual findings include: TP53 mutation in a juvenile pilocytic astrocytoma; TP53 and PTEN mutations in a de novo glioblastoma, a gliosarcoma with identical mutations in gliomatous and sarcomatous components, and an infratentorial anaplastic astrocytoma with an earlier supratentorial grade II astrocytoma bearing the same TP53 mutation but not the PTEN mutation or loss of heterozygosity (LOH) of 10q23.
Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic protein-positively stained tumor cells may have a higher tendency to progress.
To explore the possibility for a novel therapeutic approach we measured the effect of the epidermal growth factor receptor (EGFR) small molecule tyrosine kinase inhibitor gefitinib on five JPA primary cell-cultures.
Importantly, gain of function abnormalities in components of MAP-Kinase signalling are potentially present in all JPA making this tumour amenable to therapeutic targeting of this pathway.