A Mortality Gene(s) for the Human Adenocarcinoma Line HeLa Maps to a 130-kb Region of Human Chromosome 4q22-q23

Abstract

Human chromosome 4 was previously shown to elicit features of senescence when introduced into cell lines that map to complementation group B for senescence, including HeLa cells. Subsequently, a DNA segment encoding the pseudogene Mortality Factor 4 (MORF4) was shown to reproduce some of the effects of the intact chromosome 4 and was suggested to be a candidate mortality gene. We have identified multiple MORF4 alleles in several cell lines and tissues by sequencing and have failed to detect any cancer-specific mutations in three of the complementation group B lines (HeLa, T98G, and J82). Furthermore, MORF4 was heterozygous in these lines. These results question whether MORF4 is the chromosome 4 mortality gene. To map other candidate mortality gene(s) on this chromosome, we employed microcell-mediated monochromosome transfer to introduce either a complete copy, or defined fragments of the chromosome into HeLa cells. The introduced chromosome 4 fragments mapped the mortality gene to a region between the centromere and the marker D4S2975 (4q27), thus excluding MORF4, which maps to 4q33-q34.1. Analysis of microsatellite markers on the introduced chromosome in 59 immortal segregants identified a frequently deleted region, spanning the markers BIR0110 and D4S1557. This defines a new candidate interval of 130 kb at 4q22-q23.