Learning about the Importance of Mutation Prevention from Curable Cancers and Benign Tumors

Abstract

Some cancers can be cured by chemotherapy or radiotherapy, presumably because they are derived from those cell types that not only can die easily but also have already been equipped with mobility and adaptability, which would later allow the cancers to metastasize without the acquisition of additional mutations. From a viewpoint of biological dispersal, invasive and metastatic cells may, among other possibilities, have been initial losers in the competition for resources with other cancer cells in the same primary tumor and thus have had to look for new habitats in order to survive. If this is really the case, manipulation of their ecosystems, such as by slightly ameliorating their hardship, may prevent metastasis. Since new mutations may occur, especially during and after therapy, to drive progression of cancer cells to metastasis and therapy-resistance, preventing new mutations from occurring should be a key principle for the development of new anticancer drugs. Such new drugs should be able to kill cancer cells very quickly without leaving the surviving cells enough time to develop new mutations and select resistant or metastatic clones. This principle questions the traditional use and the future development of genotoxic drugs for cancer therapy.

Protein multiplicity can lead to misconduct in western blotting and misinterpretation of immunohistochemical staining results, creating much conflicting data

“…The reasons for why there are only as few as 20,000 genes in the human genome are multiple, including mRNA and protein multiplicities that allow the genome to be much smaller than our previous expectation but in the meantime require that most genes have many different and even opposite functions, as one of us has previously expounded (Lou et al 2014;Yuan et al 2012;Jia et al 2015;Wang et al 2016). For instance, the short isoform of the Bcl-X gene, i.e.…”

“…Even different subcellular locations of a protein may have opposite functions. For example, in its location at the inner membrane of mitochondria, cytochrome c functions to power the cell and thus to sustain the cell's life by participating in ATP production, but, when it relocates to the cytosol in a stressed situation, it triggers stress-induced cell death that is widely mistaken as apoptosis (Liao and Dickson 2003;Liao 2005;Liu et al 2013;Wang et al 2016).…”

Transcriptional-Readthrough RNAs Reflect the Phenomenon of “A Gene Contains Gene(s)” or “Gene(s) within a Gene” in the Human Genome, and Thus Are Not Chimeric RNAs

“…A caveat needs to be given that many genetic alterations, as often seen in genetic diseases and tumors [ 19 , 20 , 21 , 22 , 23 , 24 ], can also lead to the formation of the abovementioned three categories of RNA in pathological situations. Indeed, some genetic alterations can cause fusion of two genes into one [ 15 , 16 , 17 , 18 ], and the fusion gene can be transcribed to two-gene RNAs in the same way as other genes [ 5 , 6 ].…”

“…This number is astonishing, considering that the human genome contains only about 20,000 protein-coding genes [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], although the number of genes may be much larger if noncoding genes are included and if readthrough genomic loci are considered as newly-identified genes and are included, as we have suggested before [ 6 ]. Many fusion RNAs derived from fusion genes formed due to genetic alterations [ 15 , 16 , 17 , 18 ], seen mainly in genetic diseases and tumors [ 19 , 20 , 21 , 22 , 23 , 24 ], have also been identified and are, peculiarly, renamed as chimeras, as they also contain sequences of two genes [ 5 , 6 ]. This reclassification of fusion RNAs to tout their novelty and importance seems unnecessary, as they belong to an ancient research sphere the importance of which has already been recognized for roughly six decades, since 1959, when the Philadelphia chromosome and its-encoded fusion genes were identified [ 25 , 26 , 27 , 28 , 29 , 30 ].…”

The well-accepted notion that gene amplification contributes to increased expression still remains, after all these years, a reasonable but unproven assumption

“…Mechanistically, this occurs likely via DNA recombination during cell division and presumably because the cells are no longer under the selective pressure in the culture,[ 30 ] and such removal of the amplified copy or copies is more often seen, and can be much easily verified in bacteria. [ 31 ] Therefore, although it is still not quite clear why some cancer cases show decreases in the expression and the gene dose of some oncogenes, it may be related to growth advantage,[ 3 32 33 34 ] which may mechanistically vary among cases. It is also possible that the paternally and maternally derived alleles are actually suppressed while the amplified alleles are activated and overexpressed, which may end up with a net result of little change in the expression level.…”