KI-RAS MUTATION AS MOLECULAR MARKER FOR CARCINOMA OF THE PANCREAS

More than 90% of tumours of the pancreas have mutations on codon 12 of the Ki-ras oncogene. Cellular DNA from pancreatic secretions and fine-needle biopsies, obtained from 69 patients (41 men, 28 women), were amplified by the polymerase chain reaction (PCR) to demonstrate this characteristic marker. All these patients had undergone endoscopic retrograde pancreatography for suspected pancreatitis or carcinoma of the pancreas. Two different methods were developed to demonstrate the mutations. With the aid of one of these methods, enrichment PCR with analysis of the restriction fragment length (FL), mutations on codon 12 of the Ki-ras gene were demonstrated in unstimulated pancreatic secretions of 29 of 33 patients with pancreatic carcinoma. Ah eleven fine-needle biopsies that had been cytologically examined showed the tumour-specific mutation. After direct sequencing of enrichment PCR a codon 12 mutation was demonstrated in pancreatic secretion from 21 of 24 patients and with the single strand conformation polymorphism analysis in 17 of 33 patients. In two of these 33 patients two different Ki-ras mutations were discovered. No mutations were found in acute inflammations or stone disease, while in five patients with chronic pancreatitis mutations were demonstrated only in those two patients in whom histological examination had revealed precancerous mucinous hyperplasia. - This investigation indicates that codon 12 mutations of the Ki-ras gene, found after PCR in pancreatic secretion and biopsies, constitute a sensitive and specific tumour marker whose clinical value is being assessed.