Pericentric inversion of chromosome 1: frequency and possible association with cancer

Request reprints from: Dr. N.B. Atkin, Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN (England). Paired unstained spheres are frequently, though not constantly, seen at the centromeres of human chromosomes (Lubs and Blitman, 1967), and they may indeed represent these structures or their associated proteins (Evans and Ross, 1974). In a recent study it was found that heteromorphism for the size of the C-bands of the No. 1 chromosomes was significantly more common in patients with malignant disease than in controls (Atkin, 1977); further cases have now been studied and, in all, 41 out of 76 (54 %) malignant cases show the heteromorphism, as compared with 22 out of 68 (32 %) controls. In the course of this study it has been noted that, where the heteromorphism is present, part of the C-band of the No. 1 chromosome with the greater amount of hetero-chromatin sometimes extends onto the short arm, suggesting that a pericentric inversion is present. This observation is based on the presence of unstained spheres at the centromere region. The present report is concerned with the frequency of pericentric inversions of the No. 1 chromosomes and includes evidence for such an inversion in one of the No. 1 chromosomes of six patients with malignant disease and one with a nonmalignant condition who are not heteromorphic for C-band size. Four of the six patients have carcinoma of the ovary, and the presence of this phenomenon in three of these has been briefly reported (Atkin and Pickthall, 1977); the other two have Hodgkin’s disease. Supported by a grant from the Cancer Research Campaign. Brief Report 181 Chromosome preparations were made from normal cells (mostly cultured lymphocytes) as previously described (Atkin, 1977) and were C-banded by the BSG technique (Sumner, 1972). Observations were made with a Zeiss Photomicroscope (planapochromat X100 1.4 NA objective); 144 individuals, including 76 cancer patients, were available for study. Cases were assessed for the presence of an inversion wherever there were at least 10 “suitable” metaphases; the latter were defined as those in which the No. 1 chromosomes were not too contracted (at least 7 μm in length) or angled at the centromere, and either one or two spheres were visible at the centromeric region of each chromosome. On the chromosome with the inversion, the sphere or spheres were situated along the C-band at a distance of at least l/3rd of its length from either end, usually opposite an indentation. Generally, consistent results were obtained on each case; in those that were considered positive for a pericentric inversion,