C-Ki-ras mutations in peripheral blood of pancreatic cancer patients: a marker for early tumor metastasis.
OBJECTIVE
To determine the incidence of circulating minimal malignant clone (CMMC) (harboring c-Ki-ras-2 mutation) in peripheral blood (PB) samples of untreated pancreatic cancer using polymerase chain reaction (PCR) analysis of c-Ki-ras-2 oncogene.


METHODS
Experiments were carried out in fresh tumor, peritoneal washings (PW), and PB samples of untreated pancreatic adenocarcinoma patients (both resectable and unresectable). Samples were taken from 16 patients diagnosed with pancreatic adenocarcinoma for the PCR analysis of mutated c-Ki-ras oncogene. Five tumor samples, 15 PB samples, and 3 PW samples were analyzed for point mutation of the c-Ki-ras gene at codon 12.


RESULTS
Out of five tumor samples analyzed for c-Ki-ras mutation, four were positive at the 12th codon. Out of total 15 PB samples, nine were positive for the c-Ki-ras point mutation at the 12th codon. All the positive PB samples showed a base substitution from GGT to GAT in the second position of the 12th codon. Out of three PW samples, two showed mutation at the second position from GGT to GAT similar to their PB and tumor samples.


CONCLUSIONS
Our study indicated the presence of the tumor cells (CMMC) in PB of pancreatic adenocarcinoma that can be identified by PCR analysis of c-Ki-ras oncogene. Patients with presence of CMMC in PB and mutation in PW had aggressive tumors that responded poorly to treatment.
Mohiuddin
M
M
Department of Radiation Medicine, University of Kentucky, Lexington 40536-0084, USA.
Ahmed
M M
MM
Venkatasubbarao
K
K
D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000556:secondary*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics*; D017354:Point Mutation
D003062:Codon; D004273:DNA, Neoplasm