Journal of Clinical & Experimental Pathology
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Tumour cell populations over time often lose expression of differentiation markers per cell in parallel with diminution in
specialisation (1) due to mutations � accumulating through �karyo-unstable� phenotype (�unstable aneuploidy�) and �mutator�
phenotype (2) � in the relevant genes. Nevertheless, tumour cell populations which accumulate mutations sufficiently to lose
differentiation markers should also lose viability-essential genes and become extinct.
In the 1960s, HJ Muller (3) proposed that mutation-susceptible sexually-reproducing organisms may avoid extinction by
crossing-over of chromosomes during meiosis. This crossing over allows good copies of viability-essential genes to be exchanged
for mutant copies in some gametes, which lead to new non-mutant individuals. The present author (4) has suggested that in the
immortality of tumour cell populations, unequal distributions of chromosomes in anaphase play a similar role. These �asymmetric
mitoses� may create the immortal tumour cells by delivering to them extra good copies of viability-essential genes.
This scenario may also explain (i) different degrees of expression of differentiation, (ii) focality of expression of differentiation,
and (iii) lack of correlation between numbers of gene copies and marker production by tumour cells (5).
(1) Midiri G et al. Cancer 1985 55: 2624-9.
(2) Loeb LA et al. Cancer Res. 2008 68:3551-7.
(3) Muller HJ. Mutat Res 1964 1: 2-9.
(4) Bignold LP. Cancer Genet Cytogenet, 2007 178: 173-4.
(5) Mayr D et al. Virchow�s Arch 2009 454:241-8
Leon Bignold graduated in medicine from the University of Western Australia in 1971, completed a research doctorate 1978, qualified as a histopathologist in 1980 and has been working in academic and diagnostic pathology ever since. He has published over 70 scientific papers and edited vol 96 of EXS (Cancer: Cell Structures, Carcinogenesis and Genomic Instability, Birkh?user, 2006). With colleagues, he has published a volume (Birkh?user, 2007) on David Paul Hansemann (1858-1920), who was the first to suggest a chromosomal theory of cancer, and another on Rudolf Virchow (Birkh?user, 2008). Dr Bignold is currently completing a volume on genomic models for complex clinical, pathological and therapeutic aspects of tumors.
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