Chromatin patterns associated with lung adenocarcinoma progression
Brooke R Druliner1, Justin A Fincher, Brittany S Sexton
1Department of Biological Science, Florida State University, Tallahassee, FL, USA.
Cell Cycle (Georgetown, Tex.)
|April 20, 2013
Summary
Chromatin structure changes during lung adenocarcinoma progression. Low-grade cancers show altered nucleosome distribution, while high-grade tumors exhibit large-scale chromosomal changes, offering new diagnostic and therapeutic markers.
Area of Science:
- Oncology
- Epigenetics
- Genomics
Background:
- Lung adenocarcinoma development involves genetic and epigenetic changes.
- The role of chromatin structure in malignant transformation is not well understood.
Purpose of the Study:
- To analyze genome-wide chromatin structure in normal and lung adenocarcinoma tissues.
- To identify chromatin-based patterns associated with cancer grade and stage.
- To develop a model for chromatin structure changes during lung cancer progression.
Main Methods:
- Systematic nucleosome distribution and chromatin accessibility microarray mapping.
- Analysis of genome-wide chromatin structure from normal tissues and primary lung adenocarcinoma.
- Comparison of chromatin patterns across different cancer grades and stages.
Main Results:
- Low-grade lung adenocarcinomas showed distinct nucleosome distributions but similar chromatin accessibility compared to normal tissue.
- High-grade lung adenocarcinomas exhibited fewer nucleosome distribution differences.
- Significant disruptions in chromosomal accessibility were observed in high-grade, high-stage tumors.
Conclusions:
- Chromatin structure undergoes significant changes during lung adenocarcinoma progression.
- A model linking nucleosome distribution changes to low-grade and chromosomal changes to high-grade tumors was developed.
- This strategy may identify novel chromatin-based biomarkers for cancer diagnosis, prognosis, and therapy.
Related Concept Videos
Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Chromatin Position Affects Gene Expression
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...
Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
