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Updated: Jul 13, 2026
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Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies
Published on: April 11, 2016
Cancer genome sequencing: the challenges ahead
1Center for Molecular Medicine and Genetics, Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA. hheng@med.wayne.edu
Summary
Cancer evolution is complex and unpredictable, driven by genome aberrations, not just mutations. Understanding cancer as a probabilistic disease is key for future research and treatment strategies.
Area of Science:
- Genomics
- Cancer Biology
- Systems Biology
Background:
- Cancer exhibits significant genetic and epigenetic heterogeneity, posing a challenge for The Cancer Genome Atlas (TCGA) Project.
- Solid tumors often display stochastic evolution patterns, unlike the predictable stepwise progression seen in hematological cancers.
Purpose of the Study:
- To analyze the dominant factors driving cancer heterogeneity.
- To evaluate the impact of current sequencing approaches in cancer research.
- To conceptualize cancer as a probabilistic disease.
Main Methods:
- Analysis of genomic aberrations as a primary driver of cancer heterogeneity.
- Comparison of evolutionary patterns in solid tumors versus hematological cancers.
- Conceptual framework development for understanding cancer evolution.
Main Results:
- Genome aberrations, rather than gene mutations, are the principal cause of cancer system heterogeneity.
- Stochastic genome variations are the driving force behind cancer evolution across multiple biological system levels.
- The effectiveness of sequencing approaches is limited when mutated genes are not the sole cause of cancer.
Conclusions:
- Cancer is fundamentally a disease of probability.
- Addressing cancer heterogeneity requires a conceptual shift, focusing on probabilistic mechanisms.
- Future cancer research and treatment strategies must consider the inherent unpredictability and complexity of cancer evolution.
Related Concept Videos
03:00Next-generation Sequencing
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
01:57Sanger Sequencing
DNA sequencing is a fundamental technique that is routinely used in the biological sciences. This method can be applied to a range of questions at different scales - from the sequencing of a cloned DNA fragment or the study of a mutation in a gene up to whole-genome sequencing. However, despite the widespread use of sequencing today, it was not until 1977 that Fredrick Sanger and his collaborators developed the chain-termination method to decode DNA sequences. It relies on the separation of a...
02:02Genomics
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
01:05Maxam-Gilbert Sequencing
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Challenges of the Maxam-Gilbert Method
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01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...