The distal region of the long arm of human chromosome 1 carries tumor suppressor activity for a human fibrosarcoma line

Abstract

Loss or inactivation of tumor suppressor genes has been implicated by indirect methods in the etiology of most human cancers. In the functional studies presented here, tumor suppressors on human chromosome 1 were investigated using microcell-mediated chromosome transfer. Translocated chromosomes from normal human cells representing most of 1q, or all of 1p and a small portion of 1q translocated onto the region of the X chromosome encoding HPRT, were transferred into human fibrosarcoma cell line HT1080. Analysis of HT1080 microcell hybrids showed a tumor suppressor activity associated with 1q. All HT1080 cells carrying transferred 1q in a ratio of 1:1 with the HT1080 genome showed a more flattened morphology and a reduced ability to form tumors in nude mice compared to parental HT1080 cells. Diploid HT1080 cells carrying a single extra 1q also had a longer population doubling time and showed a loss of ability to clone in soft agar. Tumors arose from 1q-containing clones with a longer latency period, and a large majority of the cells comprising these tumors had lost the transferred chromosome. These results indicate the presence on chromosome 1q23-qter of a tumor suppressor gene or genes that can act to suppress transformation of a human fibrosarcoma cell line.