Re: Challenging Conventional Wisdom on Cancer

From: Pim van Meurs <pimvanmeurs@yahoo.com>
Date: Thu Aug 18 2005 - 16:10:12 EDT

Panda's Thumb has investigated Wells' claims about the causes of cancer

http://www.pandasthumb.org/archives/2005/07/thats_another_f.html

There appear to be some 'problems' with his perspective.

<quote>
Biologists have known about chromosomal instability for almost as long
as we have known about the existence of genes as discrete pieces of DNA,
landmark work in the 1960’s on the Philadelphia chromosome
<http://plan2003.cancer.gov/infra/sod.htm> led to the realization that a
defective gene was at the heart of CML. Wells has the story exactly
backwards. The work on chromosomal instability and mutation in cancer
has been developing for a long time, it has long been known that
chromosomal instability was one way (along with point mutations, viral
gene disruption etc.) to generate mutant genes that will lead to cancer.
And it has been realized for several years that genetic mutations
underlie chromosomal instability
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12427531&query_hl=53>
(see also the review above).
</quote>

A good review article (although already dated) is
http://www.nature.com/nature/journal/v396/n6712/abs/396643a0_fs.html

*Genetic instabilities in human cancers*

CHRISTOPH LENGAUER^1 , KENNETH W. KINZLER^1 & BERT VOGELSTEIN^1

C. Lengauer, K. W. Kinzler and B. Vogelstein are at the Johns Hopkins
Oncology Center and B. Vogelstein is at the Howard Hughes Medical
Institute, Baltimore, Maryland 21231, USA.

Correspondence and requests for materials should be addressed to C.L.
(e-mail: lengauer@jhmi.edu).

/Nature/ *396*, 643 - 649 (17 December 1998); doi:10.1038/25292

Whether and how human tumours are genetically unstable has been debated
for decades. There is now evidence that most cancers may indeed be
genetically unstable, but that the instability exists at two distinct
levels. In a small subset of tumours, the instability is observed at the
nucleotide level and results in base substitutions or deletions or
insertions of a few nucleotides. In most other cancers, the instability
is observed at the chromosome level, resulting in losses and gains of
whole chromosomes or large portions thereof. Recognition and comparison
of these instabilities are leading to new insights into tumour pathogenesis.

<quote>The subtle sequence instabilities represented by NER-associated
instability (NIN) and MIN are rare, but another form of instability,
involving gains and losses of whole chromosomes, is likely to occur in
most human malignancies5. Karyotypic studies have shown that the
majority of cancers have lost or gained chromosomes, and
molecular studies indicate that karyotypic data actually underestimate
the true extent of such changes. Losses of heterozygosity, that is,
losses of a maternal or paternal allele in a tumour, are widespread and
are often accompanied by a gain of the opposite allele. </quote>
Received on Thu Aug 18 17:50:50 2005

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