Hypothesis: meiotic origin of trisomic neoplasms.

The gain of single additional chromosomes is a very common finding among the nonrandom abnormalities with human neoplasms. According to the current opinion, such trisomies result from a disease-related mitotic nondisjunction. In contrast, we suggest that some of these trisomies may in fact represent tissue-confined residual cell populations of meiotic origin. Our hypothesis is based on recent findings of uniparental disomies in humans (i.e., two homologous chromosomes are derived from the same parent) and on the notion that many of these disomies probably are the result of the successful correction of an initially trisomic conceptus. Thus, the trisomic neoplasm may represent the original trisomic karyotype, whereas the apparently normal disomic constitutional karyotype may be the acquired, corrected one. We propose molecular genetic strategies to test our hypothesis and suggest that constitutional uniparental disomies may be associated with an increased probability of developing neoplastic diseases characterized by trisomies for the respective chromosomes.