Understanding Cancer Through the Lens of Epigenetic Inheritance, Allele-Specific Gene Expression, and High-Throughput Technology

Lee, Maxwell P.

doi:10.3389/fonc.2019.00794

Cited by 10 publications

(7 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use-it or lose-it model accounts forwithout depending onthe role of epigenetic changes in favoring the onset of evolved adaptations (78). Epigenetic mechanisms, such as DNA methylation or small RNA-mediated epigenetic modifications, can help directly regulate the proposed coordinated antagonistic expression of P A and P B (105, 106) (Figure 1) and may be inherited (107). It can also account for the adaptive contribution of spatial and temporal non-genetic heterogeneity in populations of genetically narrow or uniform cells (28,108,109).…”

Section: The Use-it or Lose-it Model Of Adaptive Evolution Has Considerable Explanatory Power And Makes Testable Predictionsmentioning

confidence: 99%

Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution

et al. 2021

View full text Add to dashboard Cite

Although neo-Darwinian (and less often Lamarckian) dynamics are regularly invoked to interpret cancer’s multifarious molecular profiles, they shine little light on how tumorigenesis unfolds and often fail to fully capture the frequency and breadth of resistance mechanisms. This uncertainty frames one of the most problematic gaps between science and practice in modern times. Here, we offer a theory of adaptive cancer evolution, which builds on a molecular mechanism that lies outside neo-Darwinian and Lamarckian schemes. This mechanism coherently integrates non-genetic and genetic changes, ecological and evolutionary time scales, and shifts the spotlight away from positive selection towards purifying selection, genetic drift, and the creative-disruptive power of environmental change. The surprisingly simple use-it or lose-it rationale of the proposed theory can help predict molecular dynamics during tumorigenesis. It also provides simple rules of thumb that should help improve therapeutic approaches in cancer.

show abstract

Section: The Use-it or Lose-it Model Of Adaptive Evolution Has Considerable Explanatory Power And Makes Testable Predictionsmentioning

confidence: 99%

Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Epigenetics has become a primary research field over the past several years [7]. According to prior research [8], DNA and histone modification are the focuses in epigenetics. A growing number of studies have revealed various modifications of mRNAs during 5-capping and 3-tailing 4-6 under exon splicing [9], such as N6-methyladenosine (m6A) and N1-methyladenosine (m1A), as well as pseudouridine methylation [10].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of FTO Combined with CEA or CYFRA21-1 in Nonsmall Cell Lung Cancer

Shang

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. To explore the diagnostic value of FTO combined with CEA or CYFRA21-1 for nonsmall cell lung cancer (NSCLC) and to provide a theoretical basis for molecular diagnosis of NSCLC. Methods. Totally, 60 patients with nonsmall cell lung cancer (NSCLC) treated in our hospital between Feb. 2018 and Feb. 2019 were enrolled into the patient group (Pat group) and 50 healthy individuals with normal physical examination results in our hospital over the same time span into the control group (Con group). Serum of each participant was collected, and then qRT-PCR was adopted for quantification of serum FTO and the chemiluminescence method for quantification of serum CEA and CYFRA21-1. Additionally, corresponding ROC curves were drawn for diagnostic value analyses of FTO, CEA, and CYFRA21-1 in NSCLC and Cox regression analysis was performed for analysis of independent factors impacting the patients’ 3-year prognosis. Results. The Pat group presented notably higher FTO, CEA, and CYFRA21-1 levels than the Con group (all P < 0.05 ), and patients with a high FTO level faced notably higher probabilities of stage III + IV and lymph node metastasis (LNM) (both P < 0.05 ). Additionally, according to ROC curve-based analysis, with a high level in patients with NSCLC, FTO had high specificity and sensitivity in diagnosing NSCLC; joint detection of it with CEA or CYFRA21-1 demonstrated a higher sensitivity in NSCLC diagnosis and presented a higher specificity in diagnosing early NSCLC compared with detection of CEA or CYFRA21-1 alone. According to Cox regression analysis, clinical stage, LNM, and FTO were independent risk factors impacting the prognosis of patients with LC (all P < 0.05 ). Conclusion. FTO presents a high level in NSCLC cases, and joint detection of it with CEA or CYFRA21-1 delivered a higher specificity in diagnosing NSCLC in contrast to detection of CEA or CYFRA21-1 alone, so the joint detection is worth popularizing in clinical scenarios.

show abstract

“…Histone modifications together with DNA methylation and demethylation constitute the blossoming field of epigenetics, which harbors great promise as these agents are able to modify gene expression genome-wide, thus acting similarly ubiquitously as transcription factors such as p53 or MYC. Not surprisingly, these types of genes are also frequently mutated in the cancer genome, constituting one major finding of the whole-genome mutation analysis studies within TCGA projects or by other efforts [91,92].…”

Section: Pathway Pathology and Treatmentmentioning

confidence: 99%

Classification and Treatment of Diseases in the Age of Genome Medicine Based on Pathway Pathology

Petersen

2021

IJMS

View full text Add to dashboard Cite

The focus of pathology as a biomedical discipline is the identification of the pathomechanisms of diseases and the integration of this knowledge into routine diagnosis and classification. Standard tools are macroscopic and microscopic analysis complemented by immunohistochemistry and molecular pathology. So far, classification has been based on the paradigm of cellular pathology established by Rudolf Virchow and others more than 150 years ago, stating that diseases originate from diseased cells. This dogma is meanwhile challenged by the fact that cells can be fully reprogrammed. Many diseases are nowadays considered to originate from undifferentiated stem cells, induced into a diseased state by genetic or epigenetic alterations. In addition, the completion of the Human Genome Project, with the identification of more than 20.000 genes and a much higher number of gene variants and mutations, led to the concept that diseases are dominated by genetics/epigenetics rather than cells of origin. The axiom of cellular pathology, however, still holds true, as cells are the smallest animate units from which diseases originate. Medical doctors and researchers nowadays have to deal with a tremendous amount of data. The International Classification of Diseases will expand from 14.400 entities/codes in ICD-10 to more than 55.000 in ICD-11. In addition, large datasets generated by “genomics“, e.g., whole-genome sequencing, expression profiling or methylome analysis, are meanwhile not only applied in research but also introduced into clinical settings. It constitutes a major task to incorporate all the data into routine medical work. Pathway pathology may help solve this problem. It is based on the realization that diseases are characterized by three essential components: (i) cells of origin/cellular context and (ii) the alteration of cellular as well as (iii) molecular/signal transduction pathways. The concept is illustrated by elaborating on two key cellular pathways, i.e., the cellular senescence of normal cells and the immortality of cancer cells, and by contrasting single cell/single pathway diseases, such as mycoplasma and coughing pneumonia, with complex diseases such as cancer, with multiple cell types as well as multiple affected cellular and signaling pathways. Importantly, the concept of pathway pathology is not just intended to classify disease, but also to conceive new treatment modalities. This article is dedicated to Dr. Leonard Hayflick, who made basic discoveries in pathway pathology not only by identifying cells causing disease (Mycoplasma pneumoniae) and establishing cell strains for treating disease (WI-38 for viral vaccines), but also by first describing cellular senescence and immortality.

show abstract

Understanding Cancer Through the Lens of Epigenetic Inheritance, Allele-Specific Gene Expression, and High-Throughput Technology

Cited by 10 publications

References 85 publications

Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution

Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution

Diagnostic Value of FTO Combined with CEA or CYFRA21-1 in Nonsmall Cell Lung Cancer

Classification and Treatment of Diseases in the Age of Genome Medicine Based on Pathway Pathology

Contact Info

Product

Resources

About