Fig. 2 demonstrates an example of combined loss of physical and functional genome redundancy following deletion of both copies of a tumor suppressor gene.
According to Knudson's "two hit hypothesis", both copies of a tumor suppressor gene should be deleted by a mutation or allelic loss to reduce protein dosage [ 41].
Indeed, emerging evidence suggests that, at least in the case of elephants, large animals may have more copies of tumor suppressor genes (Caulin and Maley 2011).
For example, some large vertebrate species have numerous copies of tumor suppressor genes (TSGs) [ 25], e.g. the elephant (Loxodonta africana) that has twelve orthologues of the human p53 gene, a key tumor suppressor fundamental to whole genome integrity.
The cells in the small tumors lacked both copies of the M6P/IGR2R gene, but more surprisingly, a large volume of seemingly normal tissue around the lesions had only one functional copy of the gene.
In these cases, erythrocytosis is due to unregulated erythropoietin production from the tumor tissue, where both copies of VHL are mutated.
Tumor-targeting CNT constructs were synthesized by McDevitt et al. from a water-soluble precursor CNTs functionalized with covalently conjugating multiple copies of tumor-specific mAbs, radiometal-ion chelates, and fluorescent probes.
Tumor targeting single-walled carbon nanotubes (SWCNT) have been synthesized by covalent attachment multiple copies of tumor-specific monoclonal antibodies, radiation ion chelates, and fluorescent probes [ 38].
