Heng Laboratory

Article published in Translational Cancer Research

"Cancer genome evolution" by Steven D. Horne et al. has been published by the journal Translational Cancer Research and is available online.  In this article, the newly discovered pattern of cancer evolution (including the two phases of cancer evolution) and its genetic basis (including fuzzy inheritance) are described, which explain how genome and gene/epigene level heterogeneity drive macro- and micro-cellular evolution. We also suggest that understanding cancer evolution holds the key to understanding other complex diseases and evolutionary theory in general.

Article published in International Journal of Cancer

"Evolutionary mechanism unifies the hallmarks of cancer" by Steven D. Horne et al. has been published by the journal International Journal of Cancer and is available online.  In this article, the evolutionary basis for the hallmarks of cancer is discussed and the evolutionary mechanism of cancer suggested by the genome theory is employed to unify the diverse molecular mechanisms of cancer.

Dr. Heng's cancer transcriptome research featured in Genetic Engineering & Biotechnology News

In a front-page article titled "Reshaping the Cancer Transcriptome," Dr. Heng was interviewed about his genome theory of cancer evolution and his article "Unstable genomes elevate transcriptome dynamics," in which his group demonstrated the importance of transcriptome dynamics in understanding the cancer landscape.

WSU School of Medicine - Prognosis E-News

Genetic Engineering & Biotechnology News Article PDF

Article published in Frontiers in Genetics

"Stress, genomic adaptation, and the evolutionary trade-off" by Steven D. Horne et al. has been published by the journal Frontiers in Genetics and is available online.  Cells are constantly exposed to various internal and external stresses, and many ongoing investigations focus on the sources of stress, their specific molecular mechanisms and interactions, especially regarding their contributions to many common and complex diseases through defined molecular pathways. Numerous molecular mechanisms have been linked to endoplasmic reticulum stress along with many unexpected findings, drastically increasing the complexity of our molecular understanding and challenging how to apply individual mechanism-based knowledge in the clinic. A newly emergent genome theory searches for the synthesis of a general evolutionary mechanism that unifies different types of stress and functional relationships from a genome-defined system point of view. In this article, we discuss the evolutionary relationship between stress and somatic cell adaptation under physiological, pathological, and somatic cell survival conditions, the multiple meanings to achieve adaptation and its potential trade-off. In particular, we purposely defocus from specific stresses and mechanisms by redirecting attention toward studying underlying general mechanisms.

Article published in Cell Cycle

"Genome chaos: Survival strategy during crisis" by Guo Liu et al. has been published by the journal Cell Cycle and is available online.  Initially detected through cytogenetic analyses, genome chaos (a process of complex, rapid genome re-organization that results in the formation of chaotic genomes, followed by the potential to establish stable, altered genomes) has been recently confirmed by whole genome sequencing efforts, identifying multiple subtypes including "chromothripsis," "chromoplexy," "chromoanasynthesis," and "chromoangenesis."  Despite being a common phenomenon in human tumors, the mechanism and detailed aspects of the process are unknown due to the inability of observing its evolution over time in clinical samples. In this article, a simple experimental system was developed to monitor the evolutionary process of genome chaos and elucidate its mechanisms. We found that genome chaos occurs following exposure to chemotherapeutics with different mechanisms (which collectively act as stressors) and results in increased karyotypic heterogeneity and transcriptome dynamics. Rather than impacting a limited number of genes, re-organized genomes lead to new system dynamics essential for cancer evolution, acting as a mechanism of rapid, adaptive, genome based evolution which plays an essential role in promoting rapid macro-evolution of genome defined systems during crisis.

Article published in Systems Biology in Reproductive Medicine

"Ovarian cancer evolution through stochastic genome alterations: defining the genomic role in ovarian cancer" by Batoul Y. Abdallah et al. has been published by the journal Systems Biology in Reproductive Medicine and is available online.  In this article, we hypothesize that genome-mediated cancer evolution can effectively explain diverse factors that contribute to ovarian cancer; in particular, the key contribution of genome replacement can be observed during major transitions of ovarian cancer evolution including cellular immortalization, transformation, and malignancy. We briefly review major updates in the literature, illustrate how current gene-mediated research will offer limited insight into cellular heterogeneity and ovarian cancer evolution, explain a holistic framework for genome-based ovarian cancer evolution and apply it to understand the genomic dynamics of a syngeneic ovarian cancer mouse model. Finally, we employ single cell assays to further test our hypothesis, discuss predictions, and report recent findings.

Article published in International Journal of Cancer

"Unstable genomes elevate transcriptome dynamics" by Joshua B. Stevens, Ph.D. et al. has been published by the journal International Journal of Cancer and is available online.  In this article, using an immortalization model, the pattern of genome alteration and expression dynamics during somatic evolution were interrogated revealing karyotype changes influence gene expression as major alterations result in large gene expression deviation. This study illustrates the karyotype, transcriptome, and transcriptome-determined pathways are in constant flux during somatic cellular evolution, and this flux is essential for cancer formation.

Article published in Cell Cycle

"Single cell heterogeneity: Why unstable genomes are incompatible with average profiles" by Batoul Y. Abdallah et al. has been published by the journal Cell Cycle and is available online.  In this article, single-cell and population-based assays were used to describe an instability-mediated mechanism where genome heterogeneity drastically affects cell growth and cannot be accurately measured using conventional averages. We show that 1) most unstable cancer cell populations exhibit high levels of karyotype heterogeneity, where it is difficult, if not impossible, to karyotypically clone cells; and 2) by comparing stable and unstable cell populations, instability-mediated karyotype heterogeneity leads to growth heterogeneity, where outliers dominantly contribute to population growth and exhibit shorter cell cycles.

Dr. Henry H.Q. Heng posts entry for Molecular Cytogenetics journal blog

Dr. Henry H.Q. Heng's commentary titled "Henrietta Lacks (HeLa) cell genome: cell line identity and the personal privacy" has been posted on the blog of the journal Molecular Cytogenetics.  In his entry, Dr. Heng explains that there should be little concern for privacy or ownership issues regarding the HeLa cancer cell line derived from Henrietta Lacks due to the continual, drastic genomic divergence from Ms. Lacks's original genome.

Correspondence published in Nature

"Genomics: HeLa genome versus donor's genome" by Dr. Henry H.Q. Heng has been published by the journal Nature and is available online.  In this piece, Dr. Heng contends that the debate over ownership of the HeLa cancer cell line derived from Henrietta Lacks is undermined by the continual divergence of chromosomal features (i.e. karyotype) and DNA sequence in dynamic cancer cell populations.

Batoul Abdallah and Steven Horne presented at the Midwest Graduate Research Symposium

Ph.D. Candidates Batoul Abdallah and Steven Horne presented at the 4th Annual Midwest Graduate Research Symposium on April 20, 2013 at the University of Toledo. Batoul gave a poster presentation titled 'Genome heterogeneity leads to growth heterogeneity,' and Steven's poster presentation was titled 'Genome chaos - an effective mechanism for cancer evolution.' Both presentations were well-received.

Article published in Cancer and Metastasis Reviews

"Chromosomal instability (CIN): what it is and why it is crucial to cancer evolution" by Dr. Henry H.Q. Heng et al. has been published by the journal Cancer and Metastasis Reviews and is available online.

Article published in Cancer and Metastasis Reviews

"Chromosomal instability and transcriptome dynamics in cancer" by Joshua B. Stevens, Ph.D. et al. has been published by the journal Cancer and Metastasis Reviews and is available online.

Article published in Cytogenetic and Genome Research

"Karyotype heterogeneity and unclassified chromosomal abnormalities" by Dr. Henry H.Q. Heng et al. has been published by the journal Cytogenetic and Genome Research and is available online.

Article published in Cytogenetic and Genome Research

"Heterogeneity of cell death" by Joshua B. Stevens, Ph.D. et al. has been published by the journal Cytogenetic and Genome Research and is available online.

Article published in Systems Biology in Reproductive Medicine

"Genome constraint through sexual reproduction: application of 4D-Genomics in reproductive biology" by Steven D. Horne et al. has been published by the journal Systems Biology in Reproductive Medicine and is available online.

Article published in Journal of Cellular Physiology