Molecular detection of genetic alterations in the serum of colorectal cancer patients.
We have searched for the presence of genetic alterations in serum DNA obtained from 44 colorectal cancer patients. Microsatellite analysis using highly polymorphic markers revealed loss of heterozygosity and/or microsatellite instability in 35 of 44 (80%) primary tumors. No alterations were detected in the paired serum DNA. We next used an oligonucleotide-mediated mismatch ligation assay to detect tumor specific gene mutations in the serum. Among the 16 cases with a K-ras gene mutation in the tumor, the same mutation was detected in three paired serum samples. In the 10 cases with a p53 mutation in the tumor, the identical mutation was detected in seven corresponding serum samples. Comparison of the molecular analysis with clinical diagnosis of these patients revealed that none of the seven Dukes' stage B patients with a K-ras mutation in their tumors demonstrated a mutation in the serum. In contrast, five of seven stage B patients with a p53 mutation in the tumor demonstrated a mutation in the paired serum (P = 0.01, Fisher's exact test). Taken together, either a K-ras or p53 mutation was detected in the serum in 40% of the 25 patients (95% confidence interval, 21-61%), whose primary tumors contained a mutation and in 23% of the 44 patients (95% confidence interval, 12-38%) with colorectal cancer. The frequent detection of p53 mutation in the serum of patients with early stage tumors suggests a possible use of this approach for clinical prognosis and cancer monitoring of colorectal cancer patients.
Hibi
K
K
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Robinson
C R
CR
Booker
S
S
Wu
L
L
Hamilton
S R
SR
Sidransky
D
D
Jen
J
J
D000483:Alleles; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D017353:Gene Deletion; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D011379:Prognosis; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm