Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity.
Ontology highlight
ABSTRACT:
SUBMITTER: Newell F
PROVIDER: S-EPMC7567804 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity.
Newell Felicity F Wilmott James S JS Johansson Peter A PA Nones Katia K Addala Venkateswar V Mukhopadhyay Pamela P Broit Natasa N Amato Carol M CM Van Gulick Robert R Kazakoff Stephen H SH Patch Ann-Marie AM Koufariotis Lambros T LT Lakis Vanessa V Leonard Conrad C Wood Scott S Holmes Oliver O Xu Qinying Q Lewis Karl K Medina Theresa T Gonzalez Rene R Saw Robyn P M RPM Spillane Andrew J AJ Stretch Jonathan R JR Rawson Robert V RV Ferguson Peter M PM Dodds Tristan J TJ Thompson John F JF Long Georgina V GV Levesque Mitchell P MP Robinson William A WA Pearson John V JV Mann Graham J GJ Scolyer Richard A RA Waddell Nicola N Hayward Nicholas K NK
Nature communications 20201016 1
To increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed. Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS, NF1, NOTCH2, PTEN and TYRP1. Mutations and amplification of KIT are also common. ...[more]
Similar Datasets
Project description:Dengchuan cattle are the only dairy yellow cattle and endangered cattle among Yunnan native cattle breeds. However, its genetic background remains unclear. Here, we performed whole-genome sequencing of ten Dengchuan cattle. Integrating our data with the publicly available data, Dengchuan cattle were observed to be highly interbred than other cattle in the dataset. Furthermore, the positive selective signals were mainly manifested in candidate genes and pathways related to milk production, disease resistance, growth and development, and heat tolerance. Notably, five genes (KRT39, PGR, KRT40, ESR2, and PRKACB) were significantly enriched in the estrogen signaling pathway. Moreover, the missense mutation in the PGR gene (c.190T > C, p.Ser64Pro) showed a homozygous mutation pattern with higher frequency (83.3%) in Dengchuan cattle. In addition, a large number of strong candidate regions matched genes and QTLs related to milk yield and composition. Our research provides a theoretical basis for analyzing the genetic mechanism underlying Dengchuan cattle with excellent lactation and adaptability, crude feed tolerance, good immune performance, and small body size and also laid a foundation for genetic breeding research of Dengchuan cattle in the future.
| S-EPMC9001881 | biostudies-literature
Project description:Next generation sequencing has enabled systematic discovery of mutational spectra in cancer samples. Here, we used whole genome sequencing to characterize somatic mutations and structural variation in a primary acral melanoma and its lymph node metastasis. Our data show that the somatic mutational rates in this acral melanoma sample pair were more comparable to the rates reported in cancer genomes not associated with mutagenic exposure than in the genome of a melanoma cell line or the transcriptome of melanoma short-term cultures. Despite the perception that acral skin is sun-protected, the dominant mutational signature in these samples is compatible with damage due to ultraviolet light exposure. A nonsense mutation in ERCC5 discovered in both the primary and metastatic tumors could also have contributed to the mutational signature through accumulation of unrepaired dipyrimidine lesions. However, evidence of transcription-coupled repair was suggested by the lower mutational rate in the transcribed regions and expressed genes. The primary and the metastasis are highly similar at the level of global gene copy number alterations, loss of heterozygosity and single nucleotide variation (SNV). Furthermore, the majority of the SNVs in the primary tumor were propagated in the metastasis and one nonsynonymous coding SNV and one splice site mutation appeared to arise de novo in the metastatic lesion.
| S-EPMC3266028 | biostudies-literature
Project description:BackgroundAcral melanoma is a rare type of melanoma that affects world populations irrespective of skin color and has worse survival than other cutaneous melanomas. It has relatively few single nucleotide mutations without the UV signature of cutaneous melanomas, but instead has a genetic landscape characterized by structural rearrangements and amplifications. BRAF mutations are less common than in other cutaneous melanomas, and knowledge about alternative therapeutic targets is incomplete.MethodsTo identify alternative therapeutic targets, we performed targeted deep-sequencing on 122 acral melanomas. We confirmed the loss of the tumor suppressors p16 and NF1 by immunohistochemistry in select cases.ResultsIn addition to BRAF (21.3%), NRAS (27.9%), and KIT (11.5%) mutations, we identified a broad array of MAPK pathway activating alterations, including fusions of BRAF (2.5%), NTRK3 (2.5%), ALK (0.8%), and PRKCA (0.8%), which can be targeted by available inhibitors. Inactivation of NF1 occurred in 18 cases (14.8%). Inactivation of the NF1 cooperating factor SPRED1 occurred in eight cases (6.6%) as an alternative mechanism of disrupting the negative regulation of RAS. Amplifications recurrently affected narrow loci containing PAK1 and GAB2 (n = 27, 22.1%), CDK4 (n = 27, 22.1%), CCND1 (n = 24, 19.7%), EP300 (n = 20, 16.4%), YAP1 (n = 15, 12.3%), MDM2 (n = 13, 10.7%), and TERT (n = 13, 10.7%) providing additional and possibly complementary therapeutic targets. Acral melanomas with BRAFV600E mutations harbored fewer genomic amplifications and were more common in patients with European ancestry.ConclusionOur findings support a new, molecularly based subclassification of acral melanoma with potential therapeutic implications: BRAFV600E mutant acral melanomas with characteristics similar to nonacral melanomas that could benefit from BRAF inhibitor therapy, and non-BRAFV600E mutant acral melanomas. Acral melanomas without BRAFV600E mutations harbor a broad array of therapeutically relevant alterations. Expanded molecular profiling would increase the detection of potentially targetable alterations for this subtype of acral melanoma.
| S-EPMC6792090 | biostudies-literature
Project description:Nocardia is a complex and diverse genus of aerobic actinomycetes that cause complex clinical presentations, which are difficult to diagnose due to being misunderstood. To date, the genetic diversity, evolution, and taxonomic structure of the genus Nocardia are still unclear. In this study, we investigated the pan-genome of 86 Nocardia type strains to clarify their genetic diversity. Our study revealed an open pan-genome for Nocardia containing 265,836 gene families, with about 99.7% of the pan-genome being variable. Horizontal gene transfer appears to have been an important evolutionary driver of genetic diversity shaping the Nocardia genome and may have caused historical taxonomic confusion from other taxa (primarily Rhodococcus, Skermania, Aldersonia, and Mycobacterium). Based on single-copy gene families, we established a high-accuracy phylogenomic approach for Nocardia using 229 genome sequences. Furthermore, we found 28 potentially new species and reclassified 16 strains. Finally, by comparing the topology between a phylogenomic tree and 384 phylogenetic trees (from 384 single-copy genes from the core genome), we identified a novel locus for inferring the phylogeny of this genus. The dapb1 gene, which encodes dipeptidyl aminopeptidase BI, was far superior to commonly used markers for Nocardia and yielded a topology almost identical to that of genome-based phylogeny. In conclusion, the present study provides insights into the genetic diversity, contributes a robust framework for the taxonomic classification, and elucidates the evolutionary relationships of Nocardia. This framework should facilitate the development of rapid tests for the species identification of highly variable species and has given new insight into the behavior of this genus.
| S-EPMC8437295 | biostudies-literature
Project description:Metastatic cutaneous squamous cell carcinoma (CSCC) is a highly morbid disease requiring radical surgery and adjuvant therapy, which is associated with a poor prognosis. Yet, compared to other advanced malignancies, relatively little is known of the genomic landscape of metastatic CSCC. We have previously reported the mutational signatures and mutational patterns of CCCTC-binding factor (CTCF) regions in metastatic CSCC. However, many other genomic components (indel signatures, non-coding drivers, and structural variants) of metastatic CSCC have not been reported. To this end, we performed whole genome sequencing on lymph node metastases and blood DNA from 25 CSCC patients with regional metastases of the head and neck. We designed a multifaceted computational analysis at the whole genome level to provide a more comprehensive perspective of the genomic landscape of metastatic CSCC. In the non-coding genome, 3' untranslated region (3'UTR) regions of EVC (48% of specimens), PPP1R1A (48% of specimens), and ABCA4 (20% of specimens) along with the tumor-suppressing long non-coding RNA (lncRNA) LINC01003 (64% of specimens) were significantly functionally altered (Q-value < 0.05) and represent potential non-coding biomarkers of CSCC. Recurrent copy number loss in the tumor suppressor gene PTPRD was observed. Gene amplification was much less frequent, and few genes were recurrently amplified. Single nucleotide variants driver analyses from three tools confirmed TP53 and CDKN2A as recurrently mutated genes but also identified C9 as a potential novel driver in this disease. Furthermore, indel signature analysis highlighted the dominance of ID signature 13 (ID13) followed by ID8 and ID9. ID9 has previously been shown to have no association with skin melanoma, unlike ID13 and ID8, suggesting a novel pattern of indel variation in metastatic CSCC. The enrichment analysis of various genetically altered candidates shows enrichment of "TGF-beta regulation of extracellular matrix" and "cell cycle G1 to S check points." These enriched terms are associated with genetic instability, cell proliferation, and migration as mechanisms of genomic drivers of metastatic CSCC.
| S-EPMC9379253 | biostudies-literature
Project description:Assessment of mutation on expression levels Transcriptomic profile of a matched primary and metastatic acral melanoma One Primary and one metastatic acral melanoma transcript expression were assayed (no matched normal)
| S-ECPF-GEOD-28909 | biostudies-other
Project description:Mycobacterium marinum is the causative agent for the tuberculosis-like disease mycobacteriosis in fish and skin lesions in humans. Ubiquitous in its geographical distribution, M. marinum is known to occupy diverse fish as hosts. However, information about its genomic diversity is limited. Here, we provide the genome sequences for 15 M. marinum strains isolated from infected humans and fish. Comparative genomic analysis of these and four available genomes of the M. marinum strains M, E11, MB2 and Europe reveal high genomic diversity among the strains, leading to the conclusion that M. marinum should be divided into two different clusters, the "M"- and the "Aronson"-type. We suggest that these two clusters should be considered to represent two M. marinum subspecies. Our data also show that the M. marinum pan-genome for both groups is open and expanding and we provide data showing high number of mutational hotspots in M. marinum relative to other mycobacteria such as Mycobacterium tuberculosis. This high genomic diversity might be related to the ability of M. marinum to occupy different ecological niches.
| S-EPMC6089878 | biostudies-literature
Project description:Whole-genome sequencing of 217 animals from three Danish commercial pig breeds (Duroc, Landrace [LL], and Yorkshire [YY]) was performed. Twenty-six million single-nucleotide polymorphisms (SNPs) and 8 million insertions or deletions (indels) were uncovered. Among the SNPs, 493,099 variants were located in coding sequences, and 29,430 were predicted to have a high functional impact such as gain or loss of stop codon. Using the whole-genome sequence dataset as the reference, the imputation accuracy for pigs genotyped with high-density SNP chips was examined. The overall average imputation accuracy for all biallelic variants (SNP and indel) was 0.69, while it was 0.83 for variants with minor allele frequency > 0.1. This study provides whole-genome reference data to impute SNP chip-genotyped animals for further studies to fine map quantitative trait loci as well as improving the prediction accuracy in genomic selection. Signatures of selection were identified both through analyses of fixation and differentiation to reveal selective sweeps that may have had prominent roles during breed development or subsequent divergent selection. However, the fixation indices did not indicate a strong divergence among these three breeds. In LL and YY, the integrated haplotype score identified genomic regions under recent selection. These regions contained genes for olfactory receptors and oxidoreductases. Olfactory receptor genes that might have played a major role in the domestication were previously reported to have been under selection in several species including cattle and swine.
| S-EPMC7394143 | biostudies-literature
Project description:Association mapping panels represent foundational resources for understanding the genetic basis of phenotypic diversity and serve to advance plant breeding by exploring genetic variation across diverse accessions. We report the whole-genome sequencing (WGS) of 400 sorghum (Sorghum bicolor (L.) Moench) accessions from the Sorghum Association Panel (SAP) at an average coverage of 38× (25-72×), enabling the development of a high-density genomic marker set of 43 983 694 variants including single-nucleotide polymorphisms (approximately 38 million), insertions/deletions (indels) (approximately 5 million), and copy number variants (CNVs) (approximately 170 000). We observe slightly more deletions among indels and a much higher prevalence of deletions among CNVs compared to insertions. This new marker set enabled the identification of several novel putative genomic associations for plant height and tannin content, which were not identified when using previous lower-density marker sets. WGS identified and scored variants in 5-kb bins where available genotyping-by-sequencing (GBS) data captured no variants, with half of all bins in the genome falling into this category. The predictive ability of genomic best unbiased linear predictor (GBLUP) models was increased by an average of 30% by using WGS markers rather than GBS markers. We identified 18 selection peaks across subpopulations that formed due to evolutionary divergence during domestication, and we found six Fst peaks resulting from comparisons between converted lines and breeding lines within the SAP that were distinct from the peaks associated with historic selection. This population has served and continues to serve as a significant public resource for sorghum research and demonstrates the value of improving upon existing genomic resources.
| S-EPMC9544330 | biostudies-literature
Project description:Consumption of prawns as a protein source has been on the rise worldwide with seafood identified as the predominant attributable source of human vibriosis. However, surveillance of non-cholera Vibrio is limited both in public health and in food. Using a population- and market share-weighted study design, 211 prawn samples were collected and cultured for Vibrio spp. Contamination was detected in 46 % of samples, and multiple diverse Vibrio isolates were obtained from 34 % of positive samples. Whole genome sequencing (WGS) and phylogenetic analysis illustrated a comprehensive view of Vibrio species diversity in prawns available at retail, with no known pathogenicity markers identified in Vibrio parahaemolyticus and V. cholerae. Antimicrobial resistance genes were found in 77 % of isolates, and 12 % carried genes conferring resistance to three or more drug classes. Resistance genes were found predominantly in V. parahaemolyticus, though multiple resistance genes were also identified in V. cholerae and V. vulnificus. This study highlights the large diversity in Vibrio derived from prawns at retail, even within a single sample. Although there was little evidence in this study that prawns are a major source of vibriosis in the UK, surveillance of non-cholera Vibrio is very limited. This study illustrates the value of expanding WGS surveillance efforts of non-cholera Vibrios in the food chain to identify critical control points for food safety through the production system and to determine the full extent of the public health impact.
| S-EPMC8715430 | biostudies-literature