Relapse in resected lung cancer revisited: does intensified follow up really matter? A prospective study

<p>Abstract</p> <p>Background</p> <p>beside the well known predominance of distant vs. loco-regional relapse, several aspects of the relapse pattern still have not been fully elucidated.</p> <p>Methods</p> <p>prospective, controlled study on 88 patients operated for non-small cell lung cancer (NSCLC) in a 15 months period. Stage IIIA existed in 35(39.8%) patients, whilst stages IB, IIA and IIB existed in 10.2%, 4.5% and 45.5% patients respectively. Inclusion criteria: stage I-IIIA, complete resection, systematic lymphadenectomy with at least 6 lymph node groups examined, no neoadjuvant therapy, exact data of all aspects of relapse, exact data about the outcome of the treatment.</p> <p>Results</p> <p>postoperative lung cancer relapse occurred in 50(56.8%) patients. Locoregional, distant and both types of relapse occurred in 26%, 70% and 4% patients respectively. Postoperative cancer relapse occurred in 27/35(77.1%) pts. in the stage IIIA and in 21/40(52.55) pts in the stage IIB. In none of four pts. in the stage IIA cancer relapse occurred, unlike 22.22% pts. with relapse in the stage IB. The mean disease free interval in the analysed group was 34.38 ± 3.26 months.</p> <p>The mean local relapse free and distant relapse free intervals were 55 ± 3.32 and 41.62 ± 3.47 months respectively Among 30 pts. with the relapse onset inside the first 12 month after the lung resection, in 20(66.6%) pts. either T3 tumours or N2 lesions existed. In patients with N0, N1 and N2 lesions, cancer relapse occurred in 30%, 55.6% and 70.8% patients respectively</p> <p>Radiographic aspect T stage, N stage and extent of resection were found as significant in terms of survival. Related to the relapse occurrence, although radiographic aspect and extent of resection followed the same trend as in the survival analysis, only T stage and N stage were found as significant in the same sense as for survival. On multivariate, only T and N stage were found as significant in terms of survival.</p> <p>Specific oncological treatment of relapse was possible in 27/50(54%) patients.</p> <p>Conclusion</p> <p>the intensified follow up did not increase either the proportion of patients detected with asymptomatic relapse or the number of patients with specific oncological treatment of relapse.</p

New investigations around CYP11A1 and its possible involvement in an androstenone QTL characterised in Large White pigs

<p>Abstract</p> <p>Background</p> <p>Previously, in boars with extreme androstenone levels, differential expression of the <it>CYP11A1 </it>gene in the testes has been characterised. <it>CYP11A1 </it>is located in a region where a QTL influencing boar fat androstenone levels has been detected in a Large White pig population. Clarifying the role of CYP11A1 in boar taint is important because it catalyses the initial step of androstenone synthesis and also of steroid synthesis.</p> <p>Results</p> <p>A genome-wide association study located <it>CYP11A1 </it>at approximately 1300 kb upstream from SNP H3GA0021967, defining the centre of the region containing the QTL for androstenone variation. In this study, we partially sequenced the <it>CYP11A1 </it>gene and identified several new single nucleotide polymorphisms (SNP) within it. Characterisation of one animal, heterozygous for <it>CYP11A1 </it>testicular expression but homozygous for a haplotype of a large region containing <it>CYP11A1</it>, revealed that variation of <it>CYP11A1 </it>expression is probably regulated by a mutation located downstream from the SNP H3GA0021967. We analysed <it>CYP11A1 </it>expression in LW families according to haplotypes of the QTL region's centre. Effects of haplotypes on <it>CYP11A1 </it>expression and on androstenone accumulation were not concordant.</p> <p>Conclusion</p> <p>This study shows that testicular expression of <it>CYP11A1 </it>is not solely responsible for the QTL influencing boar fat androstenone levels. As a conclusion, we propose to refute the hypothesis that a single mutation located near the centre of the QTL region could control androstenone accumulation in fat by regulating the <it>CYP11A1 </it>expression.</p

Whole-genome sequencing of European autochthonous and commercial pig breeds allows the detection of signatures of selection for adaptation of genetic resources to different breeding and production systems

Background: Natural and artificial directional selection in cosmopolitan and autochthonous pig breeds and wild boars have shaped their genomes and resulted in a reservoir of animal genetic diversity. Signatures of selection are the result of these selection events that have contributed to the adaptation of breeds to different environments and production systems. In this study, we analysed the genome variability of 19 European autochthonous pig breeds (Alentejana, Bísara, Majorcan Black, Basque, Gascon, Apulo-Calabrese, Casertana, Cinta Senese, Mora Romagnola, Nero Siciliano, Sarda, Krškopolje pig, Black Slavonian, Turopolje, Moravka, Swallow-Bellied Mangalitsa, Schwäbisch-Hällisches Schwein, Lithuanian indigenous wattle and Lithuanian White old type) from nine countries, three European commercial breeds (Italian Large White, Italian Landrace and Italian Duroc), and European wild boars, by mining wholegenome sequencing data obtained by using a DNA-pool sequencing approach. Signatures of selection were identified by using a single-breed approach with two statistics [within-breed pooled heterozygosity (HP) and fixation index (FST)] and group-based FST approaches, which compare groups of breeds defined according to external traits and use/specialization/type. Results: We detected more than 22 million single nucleotide polymorphisms (SNPs) across the 23 compared populations and identified 359 chromosome regions showing signatures of selection. These regions harbour genes that are already known or new genes that are under selection and relevant for the domestication process in this species, and that affect several morphological and physiological traits (e.g. coat colours and patterns, body size, number of vertebrae and teats, ear size and conformation, reproductive traits, growth and fat deposition traits). Wild boar related signatures of selection were detected across all the genome of several autochthonous breeds, which suggests that crossbreeding (accidental or deliberate) occurred with wild boars. Conclusions: Our findings provide a catalogue of genetic variants of many European pig populations and identify genome regions that can explain, at least in part, the phenotypic diversity of these genetic resources

Runs of homozygosity provide a genome landscape picture of inbreeding and genetic history of European autochthonous and commercial pig breeds

ROHs are long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROHs and their length are indicators of the level and origin of inbreeding. Frequent common ROHs within the same population define ROH islands and indicate hotspots of selection. In this work, we investigated ROHs in a total of 1131 pigs from 20 European local pig breeds and in three cosmopolitan breeds, genotyped with the GGP Porcine HD Genomic Profiler. plink software was used to identify ROHs. Size classes and genomic inbreeding parameters were evaluated. ROH islands were defined by evaluating different thresholds of homozygous SNP frequency. A functional overview of breed-specific ROH islands was obtained via over-representation analyses of GO biological processes. Mora Romagnola and Turopolje breeds had the largest proportions of genome covered with ROH (~1003 and ~955&nbsp;Mb respectively), whereas Nero Siciliano and Sarda breeds had the lowest proportions (~207 and 247&nbsp;Mb respectively). The highest proportion of long ROH (&gt;16&nbsp;Mb) was in Apulo-Calabrese, Mora Romagnola and Casertana. The largest number of ROH islands was identified in the Italian Landrace (n = 32), Cinta Senese (n = 26) and Lithuanian White Old Type (n = 22) breeds. Several ROH islands were in regions encompassing genes known to affect morphological traits. Comparative ROH structure analysis among breeds indicated the similar genetic structure of local breeds across Europe. This study contributed to understanding of the genetic history of the investigated pig breeds and provided information to manage these pig genetic resources

Genome‐wide detection of copy number variants in European autochthonous and commercial pig breeds by whole‐genome sequencing of DNA pools identified breed‐characterising copy number states

In this study, we identified copy number variants (CNVs) in 19 European autochthonous pig breeds and in two commercial breeds (Italian Large White and Italian Duroc) that represent important genetic resources for this species. The genome of 725 pigs was sequenced using a breed‐specific DNA pooling approach (30–35 animals per pool) obtaining an average depth per pool of 42×. This approach maximised CNV discovery as well as the related copy number states characterising, on average, the analysed breeds. By mining more than 17.5 billion reads, we identified a total of 9592 CNVs (~683 CNVs per breed) and 3710 CNV regions (CNVRs; 1.15% of the reference pig genome), with an average of 77 CNVRs per breed that were considered as private. A few CNVRs were analysed in more detail, together with other information derived from sequencing data. For example, the CNVR encompassing the KIT gene was associated with coat colour phenotypes in the analysed breeds, confirming the role of the multiple copies in determining breed‐specific coat colours. The CNVR covering the MSRB3 gene was associated with ear size in most breeds. The CNVRs affecting the ELOVL6 and ZNF622 genes were private features observed in the Lithuanian Indigenous Wattle and in the Turopolje pig breeds respectively. Overall, the genome variability unravelled here can explain part of the genetic diversity among breeds and might contribute to explain their origin, history and adaptation to a variety of production systems.info:eu-repo/semantics/acceptedVersio

Islands of relationality and resilience: the shifting stakes of the Anthropocene

In recent decades island studies scholars have done much to disrupt static notions of the island form, increasingly foregrounding how islands form part of complex networks of relations, assemblages and flows. In this paper, we shift the terms of debate more explicitly to relationality in the Anthropocene. We consider the implications and challenges that a wider set of debates, particularly surrounding island ‘resilience’, concerning the Anthropocene in the social sciences and humanities pose for island studies

Dominance and parent-of-origin effects of coding and non-coding alleles at the acylCoA-diacylglycerol-acyltransferase (DGAT1) gene on milk production traits in German Holstein cows

<p>Abstract</p> <p>Background</p> <p>Substantial gene substitution effects on milk production traits have formerly been reported for alleles at the K232A and the promoter VNTR loci in the bovine acylCoA-diacylglycerol-acyltransferase 1 (<it>DGAT1</it>) gene by using data sets including sires with accumulated phenotypic observations of daughters (breeding values, daughter yield deviations). However, these data sets prevented analyses with respect to dominance or parent-of-origin effects, although an increasing number of reports in the literature outlined the relevance of non-additive gene effects on quantitative traits.</p> <p>Results</p> <p>Based on a data set comprising German Holstein cows with direct trait measurements, we first confirmed the previously reported association of <it>DGAT1 </it>promoter VNTR alleles with milk production traits. We detected a dominant mode of effects for the <it>DGAT1 </it>K232A and promoter VNTR alleles. Namely, the contrasts between the effects of heterozygous individuals at the <it>DGAT1 </it>loci differed significantly from the midpoint between the effects for the two homozygous genotypes for several milk production traits, thus indicating the presence of dominance. Furthermore, we identified differences in the magnitude of effects between paternally and maternally inherited <it>DGAT1 </it>promoter VNTR – K232A haplotypes indicating parent-of-origin effects on milk production traits.</p> <p>Conclusion</p> <p>Non-additive effects like those identified at the bovine <it>DGAT1 </it>locus have to be accounted for in more specific QTL detection models as well as in marker assisted selection schemes. The <it>DGAT1 </it>alleles in cattle will be a useful model for further investigations on the biological background of non-additive effects in mammals due to the magnitude and consistency of their effects on milk production traits.</p

Diversity across major and candidate genes in European local pig breeds

The aim of this work was to analyse the distribution of causal and candidate mutations associated to relevant productive traits in twenty local European pig breeds. Also, the potential of the SNP panel employed for elucidating the genetic structure and relationships among breeds was evaluated. Most relevant genes and mutations associated with pig morphological, productive, meat quality, reproductive and disease resistance traits were prioritized and analyzed in a maximum of 47 blood samples from each of the breeds (Alentejana, Apulo-Calabrese, Basque, Bísara, Majorcan Black, Black Slavonian (Crna slavonska), Casertana, Cinta Senese, Gascon, Iberian, Krskopolje (Krskopoljski), Lithuanian indigenous wattle, Lithuanian White Old Type, Mora Romagnola, Moravka, Nero Siciliano, Sarda, Schwa-bisch-Hallisches Schwein (Swabian Hall pig), Swallow-Bellied Mangalitsa and Turopolje). We successfully analyzed allelic variation in 39 polymorphisms, located in 33 candidate genes. Results provide relevant information regarding genetic diversity and segregation of SNPs associated to production and quality traits. Coat color and morphological trait-genes that show low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for association studies as well as breeding programs. For instance, we observed predominance of alleles that might be unfavorable for disease resistance and boar taint in most breeds and segregation of many alleles involved in meat quality, fatness and growth traits. Overall, these findings provide a detailed catalogue of segregating candidate SNPs in 20 European local pig breeds that may be useful for traceability purposes, for association studies and for breeding schemes. Population genetic analyses based on these candidate genes are able to uncover some clues regarding the hidden genetic substructure of these populations, as the extreme genetic closeness between Iberian and Alentejana breeds and an uneven admixture of the breeds studied. The results are in agreement with available knowledge regarding breed history and management, although largest panels of neutral markers should be employed to get a deeper understanding of the population’s structure and relationships

Genomic diversity, linkage disequilibrium and selection signatures in European local pig breeds assessed with a high density SNP chip

Genetic characterization of local breeds is essential to preserve their genomic variability, to advance conservation policies and to contribute to their promotion and sustainability. Genomic diversity of twenty European local pig breeds and a small sample of Spanish wild pigs was assessed using high density SNP chips. A total of 992 DNA samples were analyzed with the GeneSeek Genomic Profiler (GGP) 70 K HD porcine genotyping chip. Genotype data was employed to compute genetic diversity, population differentiation and structure, genetic distances, linkage disequilibrium and effective population size. Our results point out several breeds, such as Turopolje, Apulo Calabrese, Casertana, Mora Romagnola and Lithuanian indigenous wattle, having the lowest genetic diversity, supported by low heterozygosity and very small effective population size, demonstrating the need of enhanced conservation strategies. Principal components analysis showed the clustering of the individuals of the same breed, with few breeds being clearly isolated from the rest. Several breeds were partially overlapped, suggesting genetic closeness, which was particularly marked in the case of Iberian and Alentejana breeds. Spanish wild boar was also narrowly related to other western populations, in agreement with recurrent admixture between wild and domestic animals. We also searched across the genome for loci under diversifying selection based on FST outlier tests. Candidate genes that may underlie differences in adaptation to specific environments and productive systems and phenotypic traits were detected in potentially selected genomic regions