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

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2002-11, Vol.4 (6), p.544-550
• Main Authors: Bryce, Steven D., Morrison, Vivienne, Craig, Nicola J., Forsyth, Nicholas R., Fitzsimmons, Sara A., Ireland, Hazel, Cuthbert, Andrew P., Newbold, Robert F., Parkinson, E. Kenneth
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Cellular Senescence - genetics; chromosome 4; Chromosome Mapping; Chromosome Painting; Chromosomes, Human, Pair 4 - genetics; Chromosomes, Human, Pair 4 - metabolism; Clone Cells; complementation group B; gene mapping; Genes, Tumor Suppressor; Genetic Complementation Test; Genotype; HeLa Cells - metabolism; Humans; Loss of Heterozygosity; Mice; microcell-mediated monochromosome transfer; Microsatellite Repeats; MORF4; Phenotype; Polymorphism, Genetic; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1038/sj.neo.7900268

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.