Microsatellite alterations in serum DNA of patients with colorectal cancer.

Cell-free DNA in the blood of cancer patients has been shown to harbor microsatellite alterations frequently matching those of the primary tumors. The aim of this study was to assess the prevalence of allelic loss and instability of serum DNA microsatellites in colorectal cancers. DNA extracted from preoperative sera and microdissected tumors of 27 patients with colorectal adenocarcinoma were allelotyped for nine markers on chromosome arms 1p, 5q, 8p, 12p, 15q, 17p, 17q, and 18q. In all tumors, expression of MLH1 and MSH2 was explored immunohistochemically. Microsatellite alterations comprising loss of heterozygosity (LOH) or microsatellite instability (MSI) were present in 26 of 27 (96%) tumors and in 16 of 27 (59%) serum samples. Using stringent criteria, serum MSI was significantly (p < 0.02) more detectable than serum LOH. Of the three patients with high-grade MSI (more than two unstable loci) present in tumor and serum DNA, two had MSH2-negative tumors on immunohistochemical testing. No significant association of tumor stage or clinical outcome with serum microsatellite alterations of LOH or MSI type could be demonstrated. Although the DNA-shedding phenotype of tumors remains to be elucidated, its detection by serum DNA microsatellite analysis seems to be useful for the diagnosis and monitoring of neoplasms, including colorectal cancers with and without MSI.

Deletion mapping and linkage analysis provide strong indication for the involvement of the human chromosome region 8p12-p22 in breast carcinogenesis.

We have identified a high frequency of loss of heterozygosity (LOH) on the human chromosome region 8p12-p22 in a panel of microdissected familial (86% LOH) and sporadic (74% LOH) breast tumours. The two most frequently deleted regions were defined around marker D8S133 and in a broader centromeric region bounded by markers D8S137 and D8S339. We cannot unequivocally characterize the 8p12-p22 loss as an early or a late event in breast carcinogenesis. In parallel, we have performed linkage analysis in four German breast cancer families. A location score greater than 13.67 corresponding to a LOD score of 2.97 at the marker D8S137 has been obtained. Our results considerably strengthen the evidence for a breast cancer susceptibility gene(s) located on the short arm of the chromosome region at 8p12-p22.