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 devel opment of human ovarian cancer. Recent cytogenetic and molecular studi es have demonstrated the loss of genetic material in this region. Loss of normal growth regulatory genes may allow for the expression of tum origenicity or lead to tumor progression. Methods. The authors used DN A recombinant techniques to examine the frequency of allelic losses at four loci spanning the chromosomal region 11p15.1-11p15.5 in 40 patie nts with malignant ovarian tumors. DNA extracts from normal leukocytes and 48 tumor samples were analyzed by Southern blotting using the pol ymorphic probes pEJ6.6 (HRAS1), phins310 (INS), p20.36 (PTH), and pEM3 6 (CALCA). Results. Reduction to homozygosity in the tumor DNA was fou nd in 47.5% of the informative cases (19 of 40). Comparing the results with clinical parameters, none of the well-differentiated tumors (6 o f 40, Grade 1) and only one of the early stage tumors (6 of 40, Intern ational Federation of Gynecology and Obstetrics [FIGO] Stage I or II) showed alterations in this chromosome region. Statistical analysis rev ealed a strong correlation of rate of loss of constitutional heterozyg osity (LOH) and grade of differentiation, in the sense of higher lip a llele losses occurring in poorly differentiated tumors. Conclusions. T he authors concluded that the relatively high incidence of lip allele losses marks an important step in ovarian cancer development. Furtherm ore, statistical analysis showed that loss of lip alleles was strongly correlated with poorly differentiated ovarian cancer, indicating the location of genes involved in cellular functions associated with the d evelopment of more anaplastic tumors.