Different expression of BRAFV600E, ALK and PD-L1 in melanoma in children and adolescents : a nationwide retrospective study in Finland in 1990-2014

Background Pediatric melanoma may have a different biological background and more favorable prognosis compared with melanoma in adults. The aim of this study was to investigate melanoma in children and adolescents in the Finnish population in terms of incidence, clinical course, treatment, prognosis and BRAFV600E-, ALK- and PD-L1-positivity of the primary tumors. Materials and Methods Primary tumor samples and clinical records of all patients aged 0-19 years diagnosed with cutaneous melanoma in Finland in 1990-2014 were collected using the Finnish Cancer Registry database, Finnish hospitals and private pathology laboratories. BRAFV600E, ALK and PD-L1 were analyzed from 54 primary tumors and BRAFV600E from six metastasis samples. Results A total of 122 patients diagnosed with cutaneous melanoma were retrieved from the Cancer Registry database. The primary tumor samples of 73 patients were obtained for the review, and 56 cases were included in the study. The incidence of pediatric melanoma increased from 0.2 to 1.0/100 000 during the period 1990-2014. Spitzoid melanoma was the most common subtype (66%). The 10-year cancer-specific survival (CSS) was 88.7% in all patients. The 10-year-CSS did not differ in SLNB-positive or -negative groups. BRAFV600E was positive in 48%, ALK in 9% and PD-L1 in 2% of the tumors. BRAFV600E mutation was associated with 83% of melanoma deaths. Conclusions Young melanoma patients had more favorable prognosis and a different staining profile for BRAFV600E, ALK, and PD-L1 in primary tumor than reported in adults. SLNB status was not an indicator for survival. BRAFV600E-positive patients have worse prognosis and could benefit from surveillance and treatment similarly to adults.Peer reviewe

Leaf N resorption efficiency and litter N mineralization rate have a genotypic tradeoff in a silver birch population

Plants enhance N use efficiency by resorbing N from senescing leaves. This can affect litter N mineralization rate due to the C:N-ratio requirements of microbial growth. We examined genotypic links between leaf N resorption and litter mineralization by collecting leaves and litter from 19 Betula pendula genotypes and following the N release of litter patches on forest ground. We found significant genotypic variation for N resorption efficiency, litter N concentration, cumulative three-year patch N-input and litter N release with high broad-sense heritabilities (H-2 = 0.28-0.65). The genotype means of N resorption efficiency varied from 46% to 65% and correlated negatively with the genotype means of litter N concentration, cumulative patch N-input and litter N release. NH4+ yield under patches had a positive genotypic correlation with the cumulative patch N-input. During the first year of litter decomposition, genotypes varied from N immobilization (max 2.71 mg/g dry litter) to N release (max 1.41 mg/g dry litter), creating a genotypic tradeoff between the N conserved by resorption and the N available for root uptake during the growing season. We speculate that this tradeoff is one likely reason for the remarkably wide genotypic range of N resorption efficiencies in our birch population.Peer reviewe

Increased incidence of melanoma in children and adolescents in Finland in 1990-2014 : nationwide re-evaluation of histopathological characteristics

Background Changes in the incidence of melanoma in children and adolescents have been reported in Europe and in the USA in the recent decades. Aims The aim of this study was to examine the incidence of paediatric and adolescent melanomas in Finland in 1990-2014, and the associated clinical and histopathological characteristics to reveal temporal trends, such as changes in diagnostic sensitivity of Spitzoid melanomas. Methods Information on 122 patients diagnosed with cutaneous melanoma at 0-19 years of age in Finland in 1990-2014 were retrieved from the Finnish Cancer Registry. 73 primary melanoma archival samples were re-evaluated by two dermatopathologists to allow comparability over time. Results A 5.6% annual increase was observed in the incidence of melanoma among children and adolescents during the study period. Fifty-six tumours were confirmed as malignant melanomas in the re-evaluation. After correction for tumour misclassification in the Cancer Registry, the age-adjusted annual incidence was estimated to have increased from 1.4/1 000 000 in 1990-1994 to 5.8/1 000 000 in 2010-2014. The change in incidence was most prominent among adolescents and in Spitzoid melanoma subtype. Melanomas diagnosed 1990-2002 and 2003-2014 did not differ in terms of their clinicopathological characteristics or prognosis (hazard ratio for melanoma-related death 1.53, 95% CI 0.30 to 7.88). Spitzoid melanomas were diagnosed at a younger age, were of higher stage and had higher Clark level than other melanomas, yet the hazard ratio for death was 0.52 (95% CI 0.10 to 2.58) for Spitzoid versus other melanomas. Conclusions The incidence of cutaneous melanoma has clearly increased among the young in Finland, especially among adolescents. No evidence for overdiagnosis of Spitzoid melanomas as the underlying cause of the increased incidence was observed. Key message A nationwide retrospective re-evaluation of the cutaneous melanomas recorded in the Finnish Cancer Registry among patients aged 0-19 years in Finland in 1990-2014 revealed an approximately 4-fold increase in the incidence. The increase in the incidence was most prominent among adolescents and in the Spitzoid melanoma subtype. Our results contrast those reported in other countries, where the incidence of melanoma among adolescents has declined.Peer reviewe

Different expression of BRAFV600E, ALK and PD-L1 in melanoma in children and adolescents: a nationwide retrospective study in Finland in 1990-2014

Background Pediatric melanoma may have a different biological background and more favorable prognosis compared with melanoma in adults. The aim of this study was to investigate melanoma in children and adolescents in the Finnish population in terms of incidence, clinical course, treatment, prognosis and BRAFV600E-, ALK- and PD-L1-positivity of the primary tumors. Materials and Methods Primary tumor samples and clinical records of all patients aged 0-19 years diagnosed with cutaneous melanoma in Finland in 1990-2014 were collected using the Finnish Cancer Registry database, Finnish hospitals and private pathology laboratories. BRAFV600E, ALK and PD-L1 were analyzed from 54 primary tumors and BRAFV600E from six metastasis samples. Results A total of 122 patients diagnosed with cutaneous melanoma were retrieved from the Cancer Registry database. The primary tumor samples of 73 patients were obtained for the review, and 56 cases were included in the study. The incidence of pediatric melanoma increased from 0.2 to 1.0/100 000 during the period 1990-2014. Spitzoid melanoma was the most common subtype (66%). The 10-year cancer-specific survival (CSS) was 88.7% in all patients. The 10-year-CSS did not differ in SLNB-positive or -negative groups. BRAFV600E was positive in 48%, ALK in 9% and PD-L1 in 2% of the tumors. BRAFV600E mutation was associated with 83% of melanoma deaths. Conclusions Young melanoma patients had more favorable prognosis and a different staining profile for BRAFV600E, ALK, and PD-L1 in primary tumor than reported in adults. SLNB status was not an indicator for survival. BRAFV600E-positive patients have worse prognosis and could benefit from surveillance and treatment similarly to adults.</div

Increased incidence of melanoma in children and adolescents in Finland in 1990-2014: nationwide re-evaluation of histopathological characteristics

BackgroundChanges in the incidence of melanoma in children and adolescents have been reported in Europe and in the USA in the recent decades.AimsThe aim of this study was to examine the incidence of paediatric and adolescent melanomas in Finland in 1990-2014, and the associated clinical and histopathological characteristics to reveal temporal trends, such as changes in diagnostic sensitivity of Spitzoid melanomas.MethodsInformation on 122 patients diagnosed with cutaneous melanoma at 0-19 years of age in Finland in 1990-2014 were retrieved from the Finnish Cancer Registry. 73 primary melanoma archival samples were re-evaluated by two dermatopathologists to allow comparability over time.ResultsA 5.6% annual increase was observed in the incidence of melanoma among children and adolescents during the study period. Fifty-six tumours were confirmed as malignant melanomas in the re-evaluation. After correction for tumour misclassification in the Cancer Registry, the age-adjusted annual incidence was estimated to have increased from 1.4/1 000 000 in 1990-1994 to 5.8/1 000 000 in 2010-2014. The change in incidence was most prominent among adolescents and in Spitzoid melanoma subtype. Melanomas diagnosed 1990-2002 and 2003-2014 did not differ in terms of their clinicopathological characteristics or prognosis (hazard ratio for melanoma-related death 1.53, 95% CI 0.30 to 7.88). Spitzoid melanomas were diagnosed at a younger age, were of higher stage and had higher Clark level than other melanomas, yet the hazard ratio for death was 0.52 (95% CI 0.10 to 2.58) for Spitzoid versus other melanomas.ConclusionsThe incidence of cutaneous melanoma has clearly increased among the young in Finland, especially among adolescents. No evidence for overdiagnosis of Spitzoid melanomas as the underlying cause of the increased incidence was observed.Key messageA nationwide retrospective re-evaluation of the cutaneous melanomas recorded in the Finnish Cancer Registry among patients aged 0-19 years in Finland in 1990-2014 revealed an approximately 4-fold increase in the incidence. The increase in the incidence was most prominent among adolescents and in the Spitzoid melanoma subtype. Our results contrast those reported in other countries, where the incidence of melanoma among adolescents has declined.</p

Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch

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Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch

Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.Peer reviewe

Author Correction: Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch.

In the version of this article initially published, there was a mistake in the calculation of the nucleotide mutation rate per site per generation: 1 × 10−9 mutations per site per generation was used, whereas 9.5 × 10−9 was correct. This error affects the interpretation of population-size changes over time and their possible correspondence with known geological events, as shown in the original Fig. 4 and supporting discussion in the text, as well as details in the Supplementary Note. Neither the data themselves nor any other results are affected. Figure 4 has been revised accordingly. Images of the original and corrected figure panels are shown in the correction notice

Using long-term data to reveal the geographical variation in timing and quantity of pollen and seed production in silver and pubescent birch in Finland : Implications for gene flow, hybridization and responses to climate warming

Silver (Betula pendula) and pubescent birch (B. pubescens) are the two main broad-leaved tree species in boreal forests and Subarctic areas, with great significance for both northern societies and ecosystems. Silver birch has more economical importance as it grows taller, but pubescent birch reaches much further North. The adaptability and genetic diversity of Subarctic birch populations are assumed to derive from inter- and intraspecific hybridization. Southern pollen clouds could in turn increase the adaptability of northern populations to warming climate. In the boreal forest zone of warmer climate, incompatibility reactions may prevent interspecific hybridization and much depends on the synchrony of flowering. Direct in situ observations are, however, mostly lacking and earlier results concerning the spatial and temporal match of flowering phenology between the species are contradictory. Conclusions based on pollen catches may also be biased as the pollen of silver and pubescent birch are notoriously difficult to sort out and the geographical origin of pollen is virtually impossible to determine. Here we employ direct flowering observations and reanalyze old pollen and seed production data, collected along a South-North gradient in Finland, to shed more light on these issues. Our results suggest that interspecific hybridization is an unlikely mechanism of adaptation in silver and pubescent birch as there is no significant overlap in flowering either near Subarctic or in more southern boreal areas (covering latitudes 60-68 degrees N). Long-distance southern gene flow also unlikely has importance in the adaptation of northern populations to a warming climate as heat sum requirements for flowering in northern and southern populations are equal and northern birches are therefore not receptive at the time of southern flowering. Long-term data of pollen and seed production in turn suggest that pubescent birch is more effective in seed production through the whole South North gradient, but increasingly so towards the North. However, it appears that this difference is not due to silver birch flowering and regeneration being more sensitive to interannual variation as earlier suggested. Although there are more factors than reproduction alone that can affect species distributions, these two findings indicate that climate warming may not significantly alter the relative abundances of silver and pubescent birch in Subarctic Fennoscandia.Peer reviewe