T. Yamada et al., DETECTION OF K-RAS GENE-MUTATIONS IN PLASMA DNA OF PATIENTS WITH PANCREATIC ADENOCARCINOMA - CORRELATION WITH CLINICOPATHOLOGICAL FEATURES, Clinical cancer research, 4(6), 1998, pp. 1527-1532
We investigated the presence of K-ras gene mutation in plasma DNA and
assessed its clinical value in patients with pancreatic adenocarcinoma
, Mutations in codon 12 of the K-l as gene were examined by mutant all
ele-specific amplification method using DNA extracted from surgical sp
ecimens and plasma samples of 21 patients with pancreatic adenocarcino
ma, K-ras gene mutation was detected in 15 of 21 (71%) primary tumors.
In 9 of 15 (60%) patients with K-ras gene mutation-positive tumors, a
n identical mutation was detected in the plasma DNA, None of four pati
ents with chronic pancreatitis or five healthy subjects had such mutat
ions in plasma DNA, Tumors positive for K-ras gene mutation in plasma
DNA were significantly larger (P = 0.04) and less likely to result in
a curative cure after surgical resection (P = 0.09) than those negativ
e for the mutation. Other clinicopathological features, including age,
sex, histological type, mode of invasion, and metastasis, did not cor
relate with K-ras gene mutations in plasma DNA, Treatment resulted in
disappearance of K-ras gene mutations in plasma DNA in six of nine (67
%) patients. Three patients with a persistently positive K-ras gene mu
tation in pre-and posttreatment plasma samples were likely to show ear
ly recurrence or have a progressive disease. Our findings suggest that
K-ras gene mutation can be detected in plasma DNA of patients with pa
ncreatic adenocarcinoma, Detection of K-ras mutations in plasma may be
clinically useful for evaluating tumor burden and efficacy of treatme
nt.