Prolonged mitosis causes separase deregulation and chromosome nondisjunction

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Micronuclei from misaligned chromosomes that satisfy the spindle assembly checkpoint in cancer cells

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Genomic Studies of Hereditary Disorders and the Genetic Diversity of Siberian Populations

The review considers the results of genome research on the Russian program Human Genome carried out in the Institute of Medical Genetics (Tomsk) since 1990. The three major fields were molecular cytogenetics and chromosomal disorders, genomics of Mendelian and common diseases, and ethnogenomics of the North Asian population. Several human genes were cytogenetically mapped, and numerical and structural abnormalities associated with human diseases were studied by fluorescence hybridization. Procedures of DNA diagnosis were developed for 15 hereditary diseases. New data were obtained on the genetic heterogeneity of idiopathic hypertrophic cardiomyopathy. The genetic bases of multifactorial (atopic bronchial asthma) and infectious (tuberculosis) diseases were analyzed. The North Eurasian population (41 local populations of 21 ethnic groups) was tested for genetic diversity with numerous genetic markers, including Y-chromosomal haplotypes, autosomal microsatellites, and polymorphic Alu insertions.     

MYC Dysregulates Mitosis,Revealing Cancer Vulnerabilities

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Continuing studies on chromosomal polymorphism in a Korean natural population of Drosophila melanogaster

Investigations on the chromosomal inversion polymorphism were conducted on a Korean (Taenung) natural population of D. melanogaster during the period 1978 to 1992. A total of 66 different endemic and cosmopolitan inversions were found on both major chromosome pairs II and III. Some of them proved to be rare cosmopolitan types (2LKA, 2LNS, 2LF, 2RCy, 3LM, 3RKI, and 3RK), while others were endemics. The distribution of breakpoints for endemic and rare cosmopolitan inversions are not random along the two autosome arms.With respect to frequency changes, the 15-year survey revealed that five of the cosmopolitan types (2Lt, 2RNS, 3LP, 3RC, and 3RMo) exhibit cyclical frequency changes, whereas gene arrangement 3RP shows relatively stable frequencies. Tests for correlations between gene arrangement frequencies and several climatic variables gave no clear evidence for such relationships. Only one correlation coefficient out of 64 was statistically significant. This revised version was published online in July 2006 with corrections to the Cover Date.     

Spatiotemporal heterogeneity and clinical challenge of pancreatic neuroendocrine tumors

During the course of pancreatic neuroendocrine tumors (NETs), they generally become more heterogeneous with individual cells exhibiting distinct molecular fingerprints. This heterogeneity manifests itself through an unequal distribution of genetically-variant, tumor cell subpopulations within disease locations (i.e., spatial heterogeneity) or changes in the genomic landscape over time (i.e., temporal heterogeneity); these characteristics complicate clinical diagnosis and treatment. Effective, feasible tumor heterogeneity detection and eradication methods are essential to overcome the clinical challenges of pancreatic NETs. This review explores the molecular fingerprints of pancreatic NETs and the spectrum of tumoral heterogeneity. We then describe the challenges of assessing heterogeneity by liquid biopsies and imaging modalities and the therapeutic challenges for pancreatic NETs. In general, navigating these challenges, refining approaches for translational research, and ultimately improving patient care are available once we have a better understanding of intratumoral spatiotemporal heterogeneity.