COMPARATIVE ANALYSES OF RELATIVE ERCC3 AND ERCC6 MESSENGER-RNA LEVELSIN GLIOMAS AND ADJACENT NONNEOPLASTIC BRAIN

Nucleotide excision repair (NER) is an ordered process in nonmalignant cells, in both human and nonhuman systems. We previously reported tha t in human brain, there is discordant mRNA expression of excision repa ir cross-complementing (ERCC) 1 and ERCC2 in malignant tissues, concur rent with excellent concordance of these genes in nonmalignant tissues from the same patients. Here we have extended these studies to compar e low-grade tumors to high-grade tumors and to include ERCC3 (which li nks DNA repair with DNA transcription) and ERCC6 (which is essential f or gene-specific repair). Glial tumor and adjacent normal brain specim ens from 19 individuals were studied. Paired malignant and nonmalignan t tissues were obtained from 12 of these patients. For ERCC3, there wa s excellent concordance of mRNA expression between malignant and nonma lignant tissues from the same individuals (P = 0.003). For ERCC6, no c oncordance was observed (P = 0.314). Tumor tissue from patients with h igh-grade gliomas exhibited marked discordance of mRNA expression patt erns in situations in which good concordance was observed in tumor tis sue from low-grade gliomas. We previously established that malignant b rain tumors show increased disorder of genes in the NER process, as co mpared with nonmalignant tissues. These data suggest that increasing d isorder in the NER process may occur as cells move from low-grade to h igh-grade malignancy. (C) 1996 Wiley-Liss, Inc.