ALU-POLYMERASE CHAIN-REACTION GENOMIC FINGERPRINTING TECHNIQUE IDENTIFIES MULTIPLE GENETIC-LOCI ASSOCIATED WITH PANCREATIC TUMORIGENESIS

DNA fingerprinting can be used to detect genetic rearrangements in can cer that may be associated with activation of oncogenes and inactivati on of tumour suppressor genes. We have developed a fingerprinting stra tegy based on polymerase chain reaction (PCR) amplification of genomic DNA with primers specific for the Alu repeat sequences, which are hig hly abundant in the human genome. This has been applied to DNA from pa ncreatic cancer and paired normal samples to isolate and identify frag ments of genomic DNA rearranged in the malignant cells. These fragment s have been sequenced and used as probes to isolate hybridising clones from gridded bacteriophage P1, phage artificial chromosome, and cosmi d libraries for fluorescent in situ hybridisation mapping and the iden tification of expressed sequences. Further characterisation has identi fied a putative novel gene (ART1) that is up-regulated specifically in pancreatic cancer as well as another sequence with similarity to gene s involved in differentiation (POU domains). In conclusion, we suggest that Alu-PCR fingerprinting may be a useful technique for the identif ication of genes involved in tumourigenesis. (C) 1997 Wiley-Liss, Inc.