Mitotic chiasmata, gene density, and oncogenes.

Chromosomes with regions rich in mitotic chiasmata in Bloom syndrome (1,3,6,11,12,17,19, and 22) have been compared for various parameters to similar-sized chromosomes 2, 4, 7, 10, 9, 18, 20, and 21 with the following results: (1) The number of genes localized on the test chromosomes is significantly higher (248) than that in the control chromosomes (133). (2) The number of trisomic abortions is significantly lower (45) for the test chromosomes than for the control chromosomes (140). (3) Homogeneously stained regions in neuroblastoma lie at chiasma-containing regions on chromosome arms 1p, 6p, 17q, and 19p or q. (4) The average chiasma density of regions with at least one oncogene is 2.414, whereas that of regions containing no known oncogene is 1.137; however, the difference is not statistically significant. The association of constant cancer chromosome breaks is also in the positive direction, but is not statistically significant. Our tentative conclusion is that the chiasma-rich regions which are Q-dark and early-replicating, and therefore assumed to contain active "housekeeping" genes are extended in interphase. Thus they are available for mitotic crossing-over. In the trisomic state they act as trisomy lethals, leading to early abortions. Being gene-rich they are more likely to contain oncogenes which is reflected also in their agreement with cancer breakpoints. The very high incidence of cancer in Bloom syndrome is a further indication of the possible association of cancer-related phenomena and mitotic crossing-over.