Discordance between K-ras mutations in bone marrow micrometastases and theprimary tumor in colorectal cancer

Purpose: To study bone marrow micrometastases from colorectal cancer patien ts for the presence of K-ras mutations and to compare their genotype with t hat of the corresponding primary tumor. Patients and Methods: bilateral iliac crest aspiration wets performed in 51 patients undergoing surgery for colorectal cancer, and bone marrow microme tastases were detected by immunohistochemistry. The presence of K-ras mutat ions was determined by single-strand conformation polymorphism analysis on both primary tumors and paired bone marrow samples and was confirmed by seq uencing. Results: In six patients with primary tumor mutations, it was possible to a mplify a mutated K-ras gene also from the bone marrow sample. In three of t hose patients the pattern of K-rag mutations differed between both samples, in two patients the mutation was identical between the bone marrow and its primary tumor, and in one patient the same mutation plus a different one w ere found. Fifteen of 17 K-ras mutations found in primary tumors were locat ed in codon 12, whereas in bone marrow, five of seven mutations were found in codon 13 (P = .003), Conclusion: Our results demonstrate that, at least for K-ras mutations, dis seminated epithelial cells are not always clonal with the primary tumor and they question the malignant genotype of bone marrow micrometastases. They also indicate that different tumoral clones may be circulating simultaneous ly or sequentially in the same patient. Analysis of the type of mutations s uggests that cell dissemination might be an early evens in colorectal carci nogenesis.