Loss of constitutional heterozygosity on chromosome 11p in human ovarian cancer positive correlation with grade of differentiation

Background. There is increasing evidence suggesting that genes located on the short arm of chromosome 11 play an important role in the development of human ovarian cancer. Recent cytogenetic and molecular studies have demonstrated the loss of genetic material in this region. Loss of normal growth regulatory genes may allow for the expression of tumorigenicity or lead to tumor progression. Methods. The authors used DNA recombinant techniques to examine the frequency of allelic losses at four loci spanning the chromosomal region 11p15.1–11p15.5 in 40 patients with malignant ovarian tumors. DNA extracts from normal leukocytes and 48 tumor samples were analyzed by Southern blotting using the polymorphic probes pEJ6.6 (HRAS1), phins310 (INS), p20.36 (PTH), and pEM36 (CALCA). Results. Reduction to homozygosity in the tumor DNA was found in 47.5% of the informative cases (19 of 40). Comparing the results with clinical parameters, none of the well‐differentiated tumors (6 of 40, Grade 1) and only one of the early stage tumors (6 of 40, International Federation of Gynecology and Obstetrics [FIGO] Stage I or II) showed alterations in this chromosome region. Statistical analysis revealed a strong correlation of rate of loss of constitutional heterozygosity (LOH) and grade of differentiation, in the sense of higher 11p allele losses occurring in poorly differentiated tumors. Conclusions. The authors concluded that the relatively high incidence of 11p allele losses marks an important step in ovarian cancer development. Furthermore, statistical analysis showed that loss of 11p alleles was strongly correlated with poorly differentiated ovarian cancer, indicating the location of genes involved in cellular functions associated with the development of more anaplastic tumors.