Tumor Genome Screening by Multilocus DNA Fingerprints as Obtained by Simple Repetitive Oligonucleotide Probes

Abstract

The process of neoplastic transformation and its sequelae are generally accompanied by profound genomic alterations. Gain or loss of whole chromosomes and gross chromosomal translocations or other rearrangements are readily detectable by cytogenetic investigation [31]. In order to detect minor somatic changes such as microdeletions or point mutations, direct DNA analyses are necessary [39]. Specific oncogene amplification events can be ascertained via, for example, the Southern blot hybridization technique [4]. Cytogenetic analyses have revealed a multitude of different numerical and structural abnormalities in gliomas of high and low grades of malignancy [5, 15, 18]. The most common features are early loss of gonosomes and gain of additional copies of chromosome 7. The most frequent aberration in human gliomas is the presence of double minutes (dmin) in nearly 50% of the cases with higher malignancy grade [3, 4]. Double minutes are cytogenetic equivalents of gene amplification [11] and in human gliomas they usually coincide with amplification of the epidermal growth factor receptor (EGFR) gene [4]. Recently DNA fingerprinting has been applied to detect somatic changes in human cancer DNA [25, 28]. As in karyotyping, oligonucleotide fingerprinting allows a simultaneous survey of the alterations in the whole genome for numerous highly variable DNA loci which are scattered over the chromosomes [7]. Therefore fingerprinting may serve to supplement or sometimes even replace karyotype analysis, which is technically difficult in solid tumors and impossible when only frozen tissue is available.