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Significance of Oncogenes

Larry H. Bernstein, MD, FCAP, Curator

LPBI

Epigenetics and Cancer Causing Genes

Kleon Tona    Mar 13, 2015   https://www.linkedin.com/pulse/epigenetics-cancer-causing-genes-oncogenes-kleon-tona

I. Cancer Causing Genes?
I have read an article recently that explained cancer as just plain “bad luck.” I do not believe this to be the case. There are harmful initiators of cancer and it can be associated with unfortunate timing, exposures, poor protections, faulty adaptation and circumstances beyond control. There are approximately 2,619 known genes that are associated with cancer expression and I am confident that this number will change as more research continues. These types of genes are also called oncogenes. These genes can be directly or indirectly associated with cancer initiation, progression, expression, survival and demise.

II. Epigenetics?
Epigenetics plays an important role in the turn on or off signaling of these genes by influencing DNA protection mechanisms without altering the DNA sequencing. Epigenetics refers to high-level information residing above the genetic code. While each cell in the body is equipped with the same genetic manual, epigenetic instructions tell cells how to make a difference. These instructions determine the access to pages with genetic information by directing the way the DNA is packaged into chromatin. DNA organized in loose chromatin is readily available for gene expression. Conversely, DNA tightly packed into dense chromatin has the letters of genetic code effectively buried and unavailable for reading and transcription. Distinct epigenetic marks decide which sets of genes may be expressed and which genes are kept silent.

III. DNA Methylation Hypomethylation and Hypermethylation?
In previous articles (blogs), we discussed the methylation process of DNA. Simply, methylation is the mechanism by which DNA is in homeostasis (healthy sequencing) or in harmful dysfunctional sequencing. Hypomethylation (decreased or low) and Hypermethylation (increased or high) are the two extremes that initiate harmful consequences upon DNA and ultimately lead to and result in unfavorable conditions and change in DNA sequencing performance. Ultimately, this leads to unfavorable function and potentially bad signals altering cell health and survival, predisposing new cell lines to “bad” mutations.

DNA methylation patterns undergo complex changes in cancer. The total amount of methylated cytosine is usually decreased resulting in global (extensive) hypomethylation. Decreased cytosine methylation typically affects satellite DNA, repetitive sequences, and CpG sites. In genetics, CpG is a site where cytosine (C) lies next to guanine (G) in the DNA sequence. (The p indicates that C and G are connected by a phosphodiester bond.) Methylation of DNA occurs at any CpG site. The cause of reduced amount of methylcytosine observed in human tumors has not been determined and remains under investigation. Despite global hypomethylation, high activity of DNA methyltransferases has been detected in multiple human tumor types. This increase may be related to higher proliferation rate of malignant cells.
Besides global (extensive) hypomethylation, most cancers also show focal hypermethylation in distinct subsets of promoter-associated CpG islands as well. Affected genes are permanently silenced, since methylation marks are propagated through mitosis and are maintained in the malignant clone. Aberrant (diverging from normal) hypermethylation occurring in transformed cells serves as an alternative mechanism for inactivation of tumor suppressor genes. Hundreds to thousands of genes can be epigenetically silenced by CpG island hypermethylation in human cancer suggesting a general disturbance of epigenetic memory. Methylation affects individual cancer patients with varying extent. While some patients have minimal changes, others show concordant hypermethylation of multiple genes. This phenomenon was first described as CpG island methylator phenotype (CIMP) in colorectal cancer and confirmed in many other types of cancer and leukemia. Epigenetic DNA methylation changes in cancer appear to be considerably more frequent events than genetic mutations. Mass sequencing of more than 20,000 transcripts in breast and colorectal cancers revealed about 80 harmless and less than 15 potentially oncogenic mutations per tumor. Balanced methylation and protective epigenetics are essential in minimizing cancer-causing mutations.

IV. Not Just Bad Luck!
Cancer is, in fact, a scary diagnosis and it is unfortunate when it occurs. However, I would not term it “bad luck,” as this implies a powerless and hopeless end. The gift of life is filled with miraculous movements that defy the laws of nature. Protective epigenetics can be considered miraculous and spontaneous and is what becomes necessary to move toward favorable adaptations that increase health, longevity and survival. Moreover, it is the mechanism by which succeeding familial generations can benefit in protections against cancer. It’s not just about our own protective actions on gene expression but also for the protective adaptability of future generations. There is hope and record of individuals having spontaneous regression of cancer. I have treated many in my clinical career! Encourage the expression of your healthy genes by protective epigenetics!

Your Genetic Solution

V. For Your Interest and Exploration (2,619)