Genetic changes during immortalization of human cells

Spontaneous immortalization of fibroblasts containing an inherited mutation of one p53 allele was associated with loss of the wild-type p53 allele and loss of p16INK4 gene expression, but this combination of genetic events was insufficient for immortalization. Loss of p16INK4 expression appears to be an alternative to loss of functional retinoblastoma gene product. In all cell lines studied, immortalization was associated either with stabilization of telomere length in the presence of telomerase activity or with the acquisition of long and heterogeneous telomeres in the absence of detectable telomerase. The role of other genes, such as human stanniocalcin, in the immortalization process is under investigation. © 1995 Wiley-Liss, Inc.