Delayed development of retinoblastoma associated with loss of a maternal allele on chromosome 13.

Loss of heterozygosity (LOH) on chromosome 13, which is associated with the functional inactivation of the retinoblastoma (RB) gene, is critical for the development of RB. To date, we have found that LOH-negative tumors develop earlier than LOH-positive tumors in hereditary cases of RB, an observation which suggests that loss of one allele on chromosome 13 may be disadvantageous with respect to growth of RB tumors. In this study, the parental origin of the lost allele on chromosome 13 and the age at operation of 13 patients with non-hereditary RB tumors that had been enucleated at the same stage were studied, in an attempt to determine whether there are any differences between tumors with loss of a maternal allele on chromosome 13 and tumors with loss of a paternal allele. Six tumors had lost the maternal allele and 7 tumors had lost the paternal allele on chromosome 13. The age (average 694 days) of patients at operation in the case of tumors with loss of the paternal allele was significantly lower than the age (average 1,079 days) of patients at operation for removal of tumors with loss of the maternal allele. RB tumors that had lost the maternal allele on chromosome 13 developed later than tumors that had lost the paternal allele. The possibility is discussed that loss of the maternal allele on chromosome 13 might be disadvantageous for growth of RB tumors.