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Archived Comments for: Allelic loss on chromosome band 18p11.3 occurs early and reveals heterogeneity in breast cancer progression

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  1. Loss of TYMS in sporadic breast cancer

    Barry Barclay, CEO/Planet Biotech Inc.

    14 September 2007

    It is becoming increasingly clear that both loss of heterozygosity at 18p11.3 and amplification of TYMS at its normal locus or on extra-chromosomal elements serve not only as useful diagnostic and prognostic indicators in breast cancer as suggested here but may at least in some cases be causally related to breast tumor initiation and disease progression. Loss of TYMS gives rise to gross chromosome rearrangements including translocations, loss of chromosome arms, interstital deletions and amplifications. Thus low TYMS activity could be considered a molecular "driver" of subsequent cytogenetic events and an important early event in breast carcinogenesis that channels cells into histopathological subtypes. On the other hand amplification of TYMS (including a mutant polymorphic allele) could repress numerous genes including p53 and thus act as a tumor suppressor at least by phenocopy. Excess TYMS would overproduce thymine nucleotides including dTTP and thus create a molecular driver with a strong mutator phenotype. Thus TYMS in excess has the potential not only to act a tumor suppressor but also as proto-oncogene. It might be expected that such tumors with very high levels of TYMS would be of abrupt onset and fulminating clinical course.

    Competing interests

    Although in the private sector the author has no competing commercial interests.