Česká Genetická Banka

NATURE: 14. - 20. 9. 2012

Studies slow the human DNA clock

"Revised estimates of mutation rates bring genetic accounts of human prehistory into line with archaeological data.

The story of human ancestors used to be writ only in bones and tools, but since the 1960s DNA has given its own version of events. Some results were revelatory, such as when DNA studies showed that all modern humans descended from ancestors who lived in Africa more than 100,000 years ago. Others were baffling, suggesting that key events in human evolution happened at times that flatly contradicted the archaeology."

http://www.nature.com/news/studies-slow-the-human-dna-clock-1.11431

Genetic and epigenetic stability of human pluripotent stem cells

"Studies using high-resolution genome-wide approaches have recently reported that genomic and epigenomic alterations frequently accumulate in human pluripotent cells. Detailed characterization of these changes is crucial for understanding the impact of these alterations on self-renewal and proliferation, and particularly on the developmental and malignant potential of the cells. Such knowledge is required for the optimized and safe use of pluripotent cells for therapeutic purposes, such as regenerative cellular therapies using differentiated derivatives of pluripotent cells.In this Review, we summarize the current knowledge of the genomic and epigenomic stability of pluripotent human cells and the implications for stem cell research."

http://www.nature.com/nrg/journal/v13/n10/full/nrg3271.html

Comprehensive molecular portraits of human breast tumours

"We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer."

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11412.html