Tree allocation dynamics beyond heat and hot drought stress reveal changes in carbon storage, belowground translocation and growth.

Heatwaves combined with drought affect tree functioning with as yet undetermined legacy effects on carbon (C) and nitrogen (N) allocation. We continuously monitored shoot and root gas exchange, δ CO of respiration and stem growth in well-watered and drought-treated Pinus sylvestris (Scots pine) seedlings exposed to increasing daytime temperatures (max. 42°C) and evaporative demand.

Hot drought reduces the effects of elevated CO on tree water-use efficiency and carbon metabolism.

Trees are increasingly exposed to hot droughts due to CO -induced climate change. However, the direct role of [CO ] in altering tree physiological responses to drought and heat stress remains ambiguous. Pinus halepensis (Aleppo pine) trees were grown from seed under ambient (421 ppm) or elevated (867 ppm) [CO ].

Water availability as dominant control of heat stress responses in two contrasting tree species.

Heat waves that trigger severe droughts are predicted to increase globally; however, we lack an understanding of how trees respond to the combined change of extreme temperatures and water availability. Here, we studied the impacts of two consecutive heat waves as well as post-stress recovery in young Pseudotsuga menziesii (Mirb.) Franco (Douglas-fir) and Robinia pseudoacacia L.

TERT promoter mutations in familial and sporadic melanoma.

Cutaneous melanoma occurs in both familial and sporadic forms. We investigated a melanoma-prone family through linkage analysis and high-throughput sequencing and identified a disease-segregating germline mutation in the promoter of the telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase. The mutation creates a new binding motif for Ets transcription factors and ternary complex factors (TCFs) near the transcription start and, in reporter gene assays, caused up to twofold increase in transcription.

Integrin genes and susceptibility to human melanoma.

Integrins are transmembrane adhesion molecules that mediate cell-cell and cell-extracellular matrix attachment. Integrins regulate cell growth, proliferation, migration and apoptosis and as a consequence, can have a potential role in tumour progression and metastasis. In this study, we investigated 19 non-synonymous variants in the coding region of the human integrin genes representing 3 beta subunits and 13 alpha subunits, for their potential role in melanoma susceptibility and survival.

Association of inherited variation in Toll-like receptor genes with malignant melanoma susceptibility and survival.

The family of Toll-like receptors (TLRs) is critical in linking innate and acquired immunity. Polymorphisms in the genes encoding TLRs have been associated with autoimmune diseases and cancer. We investigated the genetic variation of TLR genes and its potential impact on melanoma susceptibility and patient survival.

Epigenetic deregulation of TCF21 inhibits metastasis suppressor KISS1 in metastatic melanoma.

Metastatic melanoma is a fatal disease due to the lack of successful therapies and biomarkers for early detection and its incidence has been increasing. Genetic studies have defined recurrent chromosomal aberrations, suggesting the location of either tumor suppressor genes or oncogenes. Transcription factor 21 (TCF21) belongs to the class A of the basic helix-loop-helix family with reported functions in early lung and kidney development as well as tumor suppressor function in the malignancies of the lung and head and neck.

Single-nucleotide polymorphisms in DNA-repair genes and cutaneous melanoma.

Single-nucleotide polymorphisms in different DNA-repair genes are reported to modulate risk of various cancers including melanoma. We genotyped DNA from 1186 melanoma patients and 1280 healthy controls for 13 different polymorphisms in eight DNA-repair genes. Data analyses showed that none of the polymorphisms except T241M XRCC3 was associated with an increased risk for cutaneous melanoma.

Somatic alterations in the melanoma genome: a high-resolution array-based comparative genomic hybridization study.

We performed DNA microarray-based comparative genomic hybridization to identify somatic alterations specific to melanoma genome in 60 human cell lines from metastasized melanoma and from 44 corresponding peripheral blood mononuclear cells. Our data showed gross but nonrandom somatic changes specific to the tumor genome. Although the CDKN2A (78%) and PTEN (70%) loci were the major targets of mono-allelic and bi-allelic deletions, amplifications affected loci with BRAF (53%) and NRAS (12%) as well as EGFR (52%), MITF (40%), NOTCH2 (35%), CCND1 (18%), MDM2 (18%), CCNE1 (10%), and CDK4 (8%).

Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk.

Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.

Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood.

Recent genome-wide association data have implicated genetic variation at 7p12.2 (IKZF1), 10q21.2 (ARIDB5), and 14q11.

Polymorphisms in the CD28/CTLA4/ICOS genes: role in malignant melanoma susceptibility and prognosis?

The appearance of vitiligo and spontaneous regression of the primary lesion in melanoma patients illustrate a relationship between tumor immunity and autoimmunity. T lymphocytes play a major role both in tumor immunity and autoimmunity. CD28, Cytotoxic T lymphocyte antigen 4 (CTLA4) and inducible costimulator (ICOS) molecules are important secondary signal molecules in the T lymphocyte activation.

A case-control study of childhood acute lymphoblastic leukaemia and polymorphisms in the TGF-beta and receptor genes.

Background: Inherited genetic variants in critical genes can putatively modulate susceptibility to childhood acute lymphoblastic leukemia (ALL).

Methods: We used allelic discrimination method to genotype 19 polymorphisms in the transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta receptor 1 (TGF-betaR1) and transforming growth factor-beta receptor 2 (TGF-betaR2) genes in 460 cases of childhood acute ALL and 552 ethnically matched controls. The genotyped polymorphisms included functional and tagging variants to cover the three genes in entirety.

Single nucleotide polymorphisms in DNA repair genes XRCC1 and APEX1 in progression and survival of primary cutaneous melanoma patients.

Single nucleotide polymorphisms, besides influencing susceptibility can potentially alter progression and survival in melanoma patients. In this study we evaluated the association of polymorphisms in the base-excision repair genes XRCC1 and APEX1 with overall survival (OS), metastasis-free survival (MFS) and survival following the first metastasis (SFM) in patients with cutaneous melanoma. We genotyped the D148E APEX1, -77 T>C XRCC1, R280H XRCC1, and R399Q XRCC1 polymorphisms in 400 German melanoma patients (Tx, N0, M0) using an allelic discrimination method.

Differential gene expression in melanocytic nevi with the V600E BRAF mutation.

We studied gene expression in 18 melanocytic nevi with and four nevi without the V600E mutation in the BRAF gene using HG-U133A 2.0 microarray with 22,277 transcripts. Data analysis revealed 92 genes up-regulated and 105 genes down-regulated in nevi with the mutation compared to nevi without mutation.

Multiple melanomas after treatment for Hodgkin lymphoma in a non-Dutch p16-Leiden mutation carrier with 2 MC1R high-risk variants.

Background: A 19-base pair germline deletion in exon 2 of the CDKN2A (cyclin-dependent kinase inhibitor 2A) gene (Leiden mutation) has been detected in Dutch families with familial melanomas. The penetrance of CDKN2A mutations varies widely and is influenced by environmental and unrelated genetic factors such as variants in the MC1R gene.

Observations: We describe a 25-year-old German woman who developed 8 invasive melanomas and 6 in situ melanomas after radiation therapy and polychemotherapy for Hodgkin lymphoma.

B-RAF and N-RAS mutations are preserved during short time in vitro propagation and differentially impact prognosis.

In melanoma, the RAS/RAF/MEK/ERK signalling pathway is an area of great interest, because it regulates tumor cell proliferation and survival. A varying mutation rate has been reported for B-RAF and N-RAS, which has been largely attributed to the differential source of tumor DNA analyzed, e.g.

ARLTS1 polymorphisms and basal cell carcinoma of the skin.

Polymorphisms in the ARLTS1 gene, a member of the Ras super-family, have been associated with susceptibility in different cancer types. The involvement of the gene in apoptotic signalling motivated us to study the role of ARLTS1 polymorphic variations in basal cell carcinoma of the skin (BCC). In a case-control study, 529 cases diagnosed with BCC and 533 controls from Hungary, Romania and Slovakia were genotyped for the S99S (297G>A), P131L (392C>T), L132L (396G>C), C148R (442T>C) and W149X (446G>A) polymorphisms in the ARLTS1 gene.

ARLTS1 variants and melanoma risk.

Variants in the tumor suppressor gene ARLTS1 (ADP-ribosylation factor-like tumor-suppressor gene 1) have been shown to influence familial cancer risk. Both Cys148Arg and Trp149Stop were associated with an increased risk of familial or high-risk familial breast cancer, respectively. We studied the impact of these gene variants on melanoma risk, investigating 351 melanoma patients and 804 control subjects.

Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding.

The transcription corepressor CtBP is often recruited to the target promoter via interaction with a conserved PxDLS motif in the interacting repressor. In this study, we demonstrate that CtBP1 was SUMOylated and that its SUMOylation profoundly affected its subcellular localization. SUMOylation occurred at a single Lys residue, Lys428, of CtBP1.

The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase.

Transcriptional repression mediated through histone deacetylation is a critical component of eukaryotic gene regulation. Here we demonstrate that the class II histone deacetylase HDAC4 is covalently modified by the ubiquitin-related SUMO-1 modifier. A sumoylation-deficient point mutant (HDAC4-K559R) shows a slightly impaired ability to repress transcription as well as reduced histone deacetylase activity.

The nucleoporin RanBP2 has SUMO1 E3 ligase activity.

Posttranslational modification with SUMO1 regulates protein/protein interactions, localization, and stability. SUMOylation requires the E1 enzyme Aos1/Uba2 and the E2 enzyme Ubc9. A family of E3-like factors, PIAS proteins, was discovered recently.