ALLELE LOSS ON CHROMOSOME-10 AND CHROMOSOME-17P AND EPIDERMAL GROWTH-FACTOR RECEPTOR GENE AMPLIFICATION IN HUMAN-MALIGNANT ASTROCYTOMA RELATED TO PROGNOSIS

Patients with high-grade astrocytomas have a poor prognosis. However, considerable variation exists within this group of patients with respe ct to post-operative survival. In order to determine whether genetic a lterations might be of help in subdividing this group, we used allele loss on chromosomes 10 and 17p and epidermal growth factor receptor (E GFR) gene amplification in the tumours as genetic parameters and deter mined their prognostic value. A series of 47 malignant (grade III and grade IV) tumours were genetically characterised, and four types of tu mours were found. Type 1 tumours had loss of heterozygosity on chromos ome arm 17p (LOH 17p) as the sole genetic alteration. Patients with th is type of tumour were relatively young (mean age 39 years) and had a median survival period of 17 months. Type 2 tumours displayed only all ele loss on chromosome 10 (LOH 10), type 3 tumours had LOH 10 + LOH 17 p and type 4 tumours contained LOH 10 + EGFR gene amplification. Patie nts with types 2, 3 and 4 tumours were older (mean ages 59, 65 and 54 years respectively) and had a shorter survival (median duration 6, 3 a nd 2 months respectively) than type 1 patients. Multivariate analysis indicated that the genetic subdivision was a significant prognostic va riable. In this study, age proved to be of minor importance with regar d to survival. Our study revealed a predominance of frontally located tumours in patients with type 1 tumours, i.e. with LOH 17p only.