The chromosomal and genetic abnormalities of cancer Which

The chromosomal and genetic abnormalities of cancer: Which one is the cause? Asilomar, Jan. 7 -9, 2007 Peter Duesberg, Alice Fabarius, Ruediger Hehlmann and Ruhong Li 1

Cancer: a genetic or a chromosomal disease? 2

The genetic cancer theory 3

The genetic cancer theory According to the NCI 2 -6 mutations cause cancer [NCI: Understanding Cancer Series, 2007]. 4

The genetic theory turns a blind eye to cancer-specific aneuploidy According to the NCI and research supported by it, mutations cause cancer by changing the cell’s morphology and “color” – but not its karyotype. 5 NCI website 2006: Karyotype normal = ca = 22 chromosome pairs + X, Y

Yet, the karyotypes of cancers are very abnormal Karyotype of a human colon cancer: Highly aneuploid, with 15 rearranged marker chromosomes Karyotype of a diploid human cell (male) 6

Karyotype of a breast cancer cell 7 MDA 231 -4

Landmarks of cancer not explained by genetic theory 8

Landmarks of carcinogenesis not explained by genetic theory 9

The genetic cancer theory also has genetic Achilles heels 10

Age-dependent incidence of cancer 11

Chromosomal cancer theory 12

Carcinogenesis as chain reaction of aneuploidizations 13

Despite questioning the orthodoxy, I expected a full absolution for this attractive new cancer theory – as on previous occasions … 14

Instead – The empire strikes back … 16

Coulter et al. now claim 6 mutations are “sufficient” for tumorigenicity 17

But Coulter also provides evidence that 6 mutations are not “sufficient” 18

The chromosomal theory offers testable explanations 19

The chromosomes of Coulter’s “converted cells” are unstable 20 Conclusion: Half of cells of Mu 6 line are randomly aneuploid.

Karyotype of an aneuploid Mu 6 cell Trisomy 7, and a marker derived from Chrom. 1 21

Chromosomal theory explains low transformation rates of “converted” cells 22

By contrast the mutation theory predicts 23

Testing spontaneous appearance of 3 -dimensional foci: about 1 per 100, 000 Mu 6 cells Mu 6 focus Mu 6 monolayer 24

Clonal aneuploidies of 8 Mu 6 foci: some stable others evolving 25

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Moreover, 3 of 8 foci are intrinsically resistant to ara-C. Mu 6 line is ara-C- sensitive. Back to Table. 28

In sum the 6 mutations were not “sufficient”. Instead… 29

So – Which one is the cause? 30

The chromosomal theory of cancer can be falsified by diploid cancers. END 31

Spontaneous focus formation of Mu 6 clone 3 Transformation rate: ~ 1 per 10^6 cells 32