Misunderstanding cancer

By: James V. Kohl | Published on: April 17, 2015

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Tumor-Only Genetic Sequencing May Misguide Cancer Treatment in Nearly Half of All Patients, Study Shows

Excerpt 1) “…they counted 382 possible tumor-related changes. But after comparing a patient’s full germline genome to his or her tumor genomes, they determined that, on average, 249 of these changes were part of the patient’s normal, inherited genetic variation and were not tumor-specific.”
Excerpt 2) “In addition to selecting personalized therapies for patients with cancer, sequencing the normal tissue genome can also increase the overall understanding of cancer, including finding cancer predisposition due to germline genome changes, says Velculescu.”
My comment: Pseudoscientific nonsense about mutations and evolution has been touted by for decades. Finally, serious scientists have begun looking at the difference between mutations and nutrient-dependent epigenetically-effected RNA-directed DNA methylation, which leads to RNA-mediated cell type differentiation via amino acid substitutions.

Interpace Diagnostics has launched a microRNA gene expression classifier for thyroid nodule identification

Excerpt: “The study, presented at ENDO 2015: The 97^th Annual Meeting & Expo of the Endocrine Society held March 5-8, 2015 in San Diego, CA, showed that benign or malignant nodules can be identified with high sensitivity and specificity resulting in clinically actionable negative predictive value (NPV) at 94% and positive predictive value (PPV) at 74%. The effect of combining nucleic acid sequencing with a gene classifier significantly improved the tests’ ability to correctly identify both benign and malignant nodules, potentially resulting in fewer unnecessary surgeries.”
Excerpt: ‘… evidence continues to accumulate clearly showing that detection of ever-increasing numbers of uncommon mutations does not by itself provide diagnostic clarity, but in fact contributes to diminishing specificity for cancer detection.”
My comment: The fact that detection of accumulated mutations does not provide diagnostic clarity should eliminate theories about accumulated mutations and evolution. How could mutations not be linked to physiopathology, but somehow lead to the evolution of biodiversity. For example, see the conclusion from Mutation-Driven Evolution: “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements” (p. 199).
In the context of what is currently known about microRNAs and cell type differentiation, that conclusion can be compared to what was presented at the annual meetings of the Society for Neuroscience. The links to presentations on “microRNA” can be viewed here: 2012 (92), 2013 (100), 2014 (107)
After Timothy Bredy’s 2012 presentation: Memories of non-coding RNA, I asked if everything that occurred “downstream” from microRNAs was determined by the microRNA/messenger RNA balance. The speaker claimed that research results during the past decade confirmed that fact.
I was somewhat embarrassed for not learning more about microRNAs until 2012, but I confirmed his claim with two others who had asked questions. Both assured me that this was a specialty field, and that few outsiders knew how much had been learned about biologically-based cause and effect. The next day, I spoke to presenters on microRNAs at several different poster presentations. I have continued to follow the research.
See, for example, from Tim Bredy and his group:
(2015) Long noncoding RNA-directed epigenetic regulation of gene expression is associated with anxiety-like behavior in mice
(2014) Methyl CpG Binding Domain Ultra-Sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation
(2014) Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation
(2013) Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation
(2013) On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory
(2012) Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders
It recently became apparent that viral microRNAs contribute to physiopathology when nutrient microRNAs fail to help repair DNA damage. The viral origins of the damage can be seen in species from microbes to man, and are being examined in the context of studies that link nutrient uptake to the immune system via theromodynamic cycles of protein biosynthesis and degradation that enable organism-level thermoregulation.
See, for example: RNA-Mediated Thermoregulation of Iron-Acquisition Genes in Shigella dysenteriae and Pathogenic Escherichia coli
Excerpt: The potential toxicity of iron and heme forces the bacterium to maintain a precise balance between the nutritional requirements for iron and the toxic effects of over-accumulation; an iron disequilibrium can lead to death of the bacterium [35]. Furthermore, it is energetically advantageous for the pathogen to produce a heme acquisition system only when it is within the host, as this is the sole environment in which the organism will encounter heme. For these reasons, the production of bacterial heme acquisition and utilization systems is often regulated in response to multiple host-associated environmental conditions including iron limitation, the presence of heme and/or host body temperature [25], [27], [30], [36], [37], [38], [39], [40], [41].
My comment: What has been learned about the bacterial immune system has since linked viruses and viral microRNAs to entropic elasticity. The availability of nutrients is linked to their anti-entropic effects on cell type differentiation via nutrient-dependent microRNAs. The nutrient-dependent microRNAs are linked from RNA-directed DNA methylation to RNA-mediated amino acid substitutions that stabilize protein folding in the organized genomes of all genera via the conserved molecular mechanisms of the biophysically constrained chemistry of nutrient-dependent protein folding. Feedback loops link nutrient uptake to the physiology of reproduction, and in animals the metabolism of nutrients to species-specific pheromones links the physiology of reproduction to fixation of the amino acid substitutions, which is manifested in their morphological and behavioral diversity.
The idea that perturbed protein folding linked from mutations to physiopathology could also somehow lead to morphological and behavioral diversity was the invention of pseudoscientists who could not explain how biodiversity arose. “[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. Assumptions, made but not verified, were taught as fact.” Mazur (2014)
The idea that cell type differentiation is RNA-mediated and pheromone-controlled in species from microbes to man is based on accurate representations of biologically-based cause and effect. See, for example: From Fertilization to Adult Sexual Behavior.
Excerpt: “Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”
Cell type differentiation is nutrient-dependent and pheromone-controlled in all cell types of all animals. The conserved molecular mechanisms of cell type differentiation are linked from the light-induced de novo creation of amino acids via the anti-entropic solar energy that controls virus-driven entropic elasticity in plants. Animals that eat plants control virus-driven entropy via nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation that link feedback loops to chromatin loops and cell type differentiation that is perturbed by mutations. The mutations are not beneficial, except in the context of ridiculous theories.
For example: MOZ and BMI1 play opposing roles during Hox gene activation in ES cells and in body segment identity specification in vivo
Excerpt: “We propose that chromatin-modifying complexes have a previously unappreciated role during the initiation phase of Hox gene expression, which is critical for the correct specification of body segment identity.”
This was reported as: Scientists uncover gene ‘architects’ responsible for body’s blueprint
Excerpt: “We know that Hox genes can be directly affected by too much vitamin A, which can cause severe deformities in the embryo,” Associate Professor Voss said. “Substances or environmental challenges that impact MOZ or BMI1 expression could affect when and where Hox genes are expressed, causing defects in the developing embryo.”

Dr Anne Voss said the research team’s discovery overturned a decades-long belief about embryonic development. “A lot of what we know about embryonic development and how it is controlled was learned from studies of fruit flies,” Associate Professor Voss said. “In this study we showed a key difference; two molecules that have only a maintenance role in fruit flies are indispensible for initiating the blueprint in mammalian development.”
My comment: The “blueprint” in mammalian development is nutrient-dependent and pheromone-controlled by the fixation of amino acid substitutions that differentiate cell types in all genera via the biophysically constrained chemistry of protein folding. The chemistry of protein folding in plants is biophysically constrained by solar energy linked to the physiology of reproduction. However, in species from microbes to man, the chemistry of protein folding varies with ecological variation that leads to nutrient-dependent pheromone-controlled survival of the species or to extinction when thermodynamic cycles of protein biosynthesis and degradation lead to mutations and physiopathology.
How epigenetic mutations can affect genetic evolution: Model and mechanism
Rapid epigenetic adaptation to uncontrolled heterochromatin spreading
Excerpt: “Our results fit into a growing body of evidence demonstrating that epigenetic regulation of gene expression enables cells to adopt a wide variety of phenotypes to adapt to external or internal stresses (Heard and Martienssen, 2014). Compared to genetic mutations, epigenetic mutations provide much faster responses. Most importantly, the effects are reversible, allowing easy reversion to normal epigenetic profiles when external stimuli disappear. In cancer cells, such epigenetic variations might result in the inactivation of tumor suppressor genes during tumorigenesis and might also enable tumor cells to survive certain therapies (Sharma et al., 2010; Kreso et al., 2013). Therefore, our work sheds light on the mechanisms underlying how a relatively stable heterochromatic profile is maintained both under normal conditions and upon heterochromatin stress and will guide future efforts to combat epigenetic adaptations that interfere with cancer treatment.”
My comment: Obviously, we have not heard the last of the pseudoscientific nonsense that has been touted by evolutionary theorists for several decades. Ridiculous theories may continue to show up in conclusions like the one above, because theorists were never taught critical thinking skills that preclude them from linking genetic mutations to increasing organismal complexity. Thus, they have no term to use to explain cell type differentiation via amino acid substitutions, and must now use ideas about “epigenetic mutations” instead of facts to explain differences in the responses of different cell types.
See also: Hox genes pattern the anterior-posterior axis of the juvenile but not the larva in a maximally-indirect developing invertebrate, Micrura alaskensis (Nemertea)
Excerpt: “Hox genes are first expressed long after the pilidium is fully formed and functional. The Hox genes are expressed in apparently overlapping domains along the AP axis of the developing juvenile in a subset of the rudiments that give rise to the juvenile trunk. Hox genes are not expressed in the larval body at any stage of development. Conclusions While the Hox genes pattern the juvenile pilidiophoran, the pilidial body, which appears to be an evolutionary novelty, must be patterned by some mechanism other than the Hox genes.”
My comment: The problem with theories about Hox genes and the evolution of morphology is this. The theory doesn’t fit into the context of molecular mechanisms that must be conserved across all species. That explains why researchers using genetic sequencing appear to have misguided cancer treatment in nearly half of all patients. The researchers don’t understand cell type differentiation and they confuse what is typical with what is pathological.