Systematic Analysis of Whole Exome Sequencing Determines RET G691S Polymorphism as Germline Variant in Melanoma

Abstract The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA to determine if RETp was 1) a germline or somatic variant, 2) more frequent in certain melanoma subtypes, and 3) frequency in brain metastasis. We examined the peripheral blood of 197 melanoma patients whom had at least one matched tumor, and 42 patients with brain metastasis. RETp was present as a germline SNP in 33% of patients. There were no significant differences in RETp frequency among the different melanoma subtypes, and RETp was not correlated with brain metastasis

Systematic Analysis of Whole Exome Sequencing Determines RET G691S Polymorphism as Germline Variant in Melanoma

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA to determine if RETp was 1) a germline or somatic variant, 2) more frequent in certain melanoma subtypes, and 3) frequency in brain metastasis. We examined the peripheral blood of 197 melanoma patients whom had at least one matched tumor, and 42 patients with brain metastasis. RETp was present as a germline SNP in 33% of patients. There were no significant differences in RETp frequency among the different melanoma subtypes, and RETp was not correlated with brain metastasis

Insight into the evolution of the Solanaceae from the parental genomes of Petunia hybrida

Petunia hybrida is a popular bedding plant that has a long history as a genetic model system. We report the whole-genome sequencing and assembly of inbred derivatives of its two wild parents, P. axillaris N and P. inflata S6. The current assemblies include 91.3% and 90.2% coverage of their diploid genomes (1.4 Gb; 2n=14) containing 32,928 and 36,697 protein-coding genes, respectively. The Petunia lineage has experienced at least two rounds of paleohexaploidization, the older gamma hexaploidy event, which is shared with other Eudicots, and the more recent Solanaceae paleohexaploidy event that is shared with tomato and other Solanaceae species. Transcription factors that were targets of selection during the shift from bee- to moth pollination reside in particularly dynamic regions of the genome, which may have been key to the remarkable diversity of floral color patterns and pollination systems. The high quality genome sequences will enhance the value of Petunia as a model system for basic and applied research on a variety of unique biological phenomena

Insight into the evolution of the Solanaceae from the parental genomes of Petunia hybrida

Petunia hybrida is a popular bedding plant that has a long history as a genetic model system. We report the whole-genome sequencing and assembly of inbred derivatives of its two wild parents, P. axillaris N and P. inflata S6. The assemblies include 91.3% and 90.2% coverage of their diploid genomes (1.4 Gb; 2n = 14) containing 32,928 and 36,697 protein-coding genes, respectively. The genomes reveal that the Petunia lineage has experienced at least two rounds of hexaploidization: the older gamma event, which is shared with most Eudicots, and a more recent Solanaceae event that is shared with tomato and other solanaceous species. Transcription factors involved in the shift from bee to moth pollination reside in particularly dynamic regions of the genome, which may have been key to the remarkable diversity of floral colour patterns and pollination systems. The high-quality genome sequences will enhance the value of Petunia as a model system for research on unique biological phenomena such as small RNAs, symbiosis, self-incompatibility and circadian rhythms

Catalytic Transfer Deuteration and Hydrodeuteration: Emerging Techniques to Selectively Transform Alkenes and Alkynes to Deuterated Alkanes

Increasing demand for deuterium-labeled organic molecules has spurred a renewed interest in selective methods for deuterium installation. Catalytic transfer deuteration and transfer hydrodeuteration are emerging as powerful techniques for the selective incorporation of deuterium into small molecules. These reactions not only obviate the use of D2 gas and pressurized reaction setups but provide new opportunities for selectively installing deuterium into small molecules. Commercial or readily synthesized deuterium donors are typically employed as easy-to-handle reagents for transfer deuteration and hydrodeuteration reactions. In this minireview, recent advances in the catalytic transfer deuteration and hydrodeuteration of alkenes and alkynes for the selective synthesis of deuterated alkanes will be discussed

Micronucleus frequency in buccal mucosa cells of patients with neurodegenerative diseases

Neurodegenerative diseases show an increase in prevalence and incidence, with the most prominent example being Alzheimer's disease. DNA damage has been suggested to play a role in the pathogenesis, but the exact mechanisms remain elusive. We enrolled 425 participants with and without neurodegenerative diseases and analyzed DNA damage in the form of micronuclei in buccal mucosa samples. In addition, other parameters such as binucleated cells, karyolytic cells, and karyorrhectic cells were quantified. No relevant differences in DNA damage and cytotoxicity markers were observed in patients compared to healthy participants. Furthermore, other parameters such as lifestyle factors and diseases were also investigated. Overall, this study could not identify a direct link between changes in buccal cells and neurogenerative diseases, but highlights the influence of lifestyle factors and diseases on the human buccal cytome

Projected health impacts from transportation noise - exploring two scenarios for 2030

This report provides outlooks to 2030 on population exposed to road, rail and aircraft noise as well as on health impacts. The outlooks comprise two scenarios, one that is conservative (i.e. the minimum implementation of existing and forthcoming regulations) and one optimistic scenario which includes a more extensive set of measures. The assessment is done in order to determine if the EU Action Plan 'Towards Zero Pollution for Air, Water and Soil' with the commitment to reduce by 2030 the share of people chronically disturbed by noise from transport by 30 % compared to 2017, could be achieved considering the outlooks calculated. Based on the overall results of this assessment, the zero-pollution action plan objective on noise is unlikely to be achieved by 2030. One of the main stoppers is the difficulty in reducing the large number of people exposed to road traffic noise. However, a combination of measures such as switching to electric vehicles in cities, reducing speed limits in cities, implementing the noise emission regulations for vehicles, and further extending low noise asphalts and noise barriers, could bring a reduction between 3-15 % of people affected by noise. Looking at individual noise sources, the assessment shows that the number of people chronically disturbed by aircraft noise could be reduced by 30 % with progressive uptake of quieter aircrafts and improved landing and taking off procedures. In terms of railway noise, it is likely that the number of people affected by railway noise will increase due to an increase of railway activity, increase of speeds, and increase of high-speed lines which offsets the benefits of silent brake regulations and improved maintenance of the tracks