According to this theory, termed the fragile site hypothesis, our genome has various sites with extensive flexibility and sequence repeats that are believed to be more difficult to replicate in fast-growing cells.
One of the most important features of mammalian chromosomal evolution is the suggestion of a non-random distribution of regions implicated in evolutionary chromosomal reorganization, the so-called "fragile-breakage" hypothesis [ 25].
With some telling examples from medicine, plain figures, and tables, Lockshin brings the reader to understand that statistics provide powerful tools for detecting correlations and also for corroborating hypotheses and discarding fragile ones: A baby born in December gets larger as the weather grows warmer.
Literature evidence supports the hypothesis that computationally identified fragile cell-cycle interactions represent efficacious targets.
If our working hypothesis is true, then fragile cell-cycle mechanisms (reaction steps) should be overrepresented among experimentally observed malfunctions underlying solid and hematological cancers.
When taken together, the retrospective cyclin E studies in breast cancer patients and the CDC25 studies support the hypothesis that malfunctions in fragile mechanisms are strongly implicated in cancer progression.
The statistical hypothesis testing demonstrated that fragile sites, light chromosome bands, telomeres, and centromeres were enriched in the ends of the amplicons (Table 1).
To explore this hypothesis, we analysed both Fragile histidine triad and mismatch repair protein (Msh2 and Mlh1) expression using immumohistochemical methods in 52 advanced colorectal carcinomas (19 well-, 17 moderately-, and 16 poorly-differentiated).
Taken this together [ 4, 12- 14], it is highly questionable whether a fragile setting relying solely on the transmission mutation hypothesis adequately describes the major processes in place or robustly represents the observed dynamics.
In addition to solidifying the role of fragile sites participating in cancer development, this study also supports the common hypothesis for the molecular basis of fragility at these sites.
