Microsatellite analysis at 10q25-q26 in Sardinian patients with sporadic endometrial carcinoma - Identification of specific patterns of genetic alteration

BACKGROUND. Loss of heterozygosity (LOH) at chromosome 10q25-q26 has been r eported previously in endometrial carcinoma (EC), suggesting the presence o f tumor suppressor gene(s). Nevertheless, frequency of genome-wide microsat ellite instability (MSI) has been demonstrated higher in EC than in other c ommon malignancy, mostly due to defective DNA mismatch repair. The authors further evaluated the role of the chromosome 10q25-q26 in endometrial tumor igenesis as well al; the clinical significance of any observed genetic alte ration in sporadic EC. METHODS, Paired normal and tumor samples from 94 Sardinian patients with sp oradic EC at various stages of disease were screened by polymerase chain re action (PCR)-based microsatellite analysis. Genomic DNA was isolated from p araffin embedded tissues and amplified by PCR using microsatellite markers spanning approximately 14 cM at 10q25-q26. Microsatellite instability was s tudied at four loci mapping to different chromosomal locations. RESULTS, Thirty-two (34%) EC patients were found negative for genetic alter ations within the 10q25-q26 region. Among the remaining 62 (66%) EC cases, the authors identified 1) a minimum consensus region of LOH of approximatel y 1 cM, between D10S610 and D10S542 markers; and 2) a subset of tumors with prevalence of instability at 10q25-q26 (10qMI+), as expression of the pres ence of a MSI+ phenotype. CONCLUSIONS, The authors' data establish the existence of significant corre lations between disease stages and 10qMI+ (with or without MSI+). However, longer followup and additional studies are required to define the clinical significance of these findings as prognostic factors. Moreover, the minimum region of LOH at 10q25-q26 will be further analyzed for identifying the pu tative tumor suppressor gene involved in EC pathogenesis. Cancer 2000;89:17 73-82, (C) 2000 American Cancer Society.