Basin scale variability of Ostreopsis spp. blooms provides evidence of effectiveness of an integrated sampling approach.

Ostreopsis spp. blooms have been occurring in the last two decades in the Mediterranean Sea in association with a variety of biotic and abiotic substrata (macroalgae, seagrasses, benthic invertebrates, sand, pebbles and rocks). Cells proliferate attached to the surfaces through mucilaginous trichocysts, which lump together microalgal cells, and can also be found in the plankton and on floating aggregates: such tychoplanktonic behavior makes the quantitative assessment of blooms more difficult than planktonic or benthic ones. Different techniques have been so far applied for quantifying cell abundances of benthic microalgae for research, monitoring and risk assessment purposes. In this context, the Benthic Dinoflagellates Integrator (BEDI), a non-destructive quantification method for benthic dinoflagellate abundances, was developed and tested within the EU ENPI-CBCMED project M3-HABs. This device allows mechanical detachment of cells without collecting the benthic substrate, providing an integrated assessment of both epiphytic and planktonic cells, i.e. of the number of cells potentially made available in the water volume from "resuspension" which could have harmful effects on other organisms (including humans). The present study confirms the effectiveness of the BEDI sampling device across different environments across the Mediterranean Sea and constitutes the first large-scale study of Ostreopsis spp. blooms magnitude in function of different macro- and meso­habitat features across the basin.

DRD1 suppresses cell proliferation and reduces EGFR activation and PD-L1 expression in NSCLC.

Dopamine (DA) acts in various key neurological and physiological processes as both a neurotransmitter and circulating hormone. Over the past several decades, the DA signaling network has been shown to regulate the progression of several types of solid tumors, and considerable evidence has shown it is a druggable pathway in the cancer cell context. However, the specific activity and effect of these pathway components appears to be tissue-type and cell-context-dependent. In the present study, expression and methylation of dopamine receptor D1 (DRD1) were measured using RNA sequencing (RNAseq) and reverse transcription polymerase chain reaction (RT-PCR) in non-small cell lung cancer (NSCLC) samples, and validated using publicly available datasets, including The Cancer Genome Atlas (TCGA). In vitro and in vivo functional experiments were performed for cell proliferation and tumor growth, respectively. Mechanistic analyses of the transcriptome and kinome in DRD1-modulated cells informed further experiments, which characterized the effects on the epidermal growth factor receptor (EGFR) pathway and programmed cell death 1 ligand 1 (PD-L1) proteins. Through these experiments, we identified the DRD1 gene as a negative regulator of disease progression in NSCLC. We show that DRD1, as well as other DA pathway components, are expressed in normal human lung tissue, and that loss of DRD1 expression through promoter hypermethylation is a common feature in NSCLC patients and is associated with worse survival. At the cellular level, DRD1 affects proliferation by inhibiting the activation of EGFR and mitogen-activated protein kinase 1/2 (ERK1/2). Interestingly, we also found that DRD1 regulates the expression of PD-L1 in lung cancer cells. Taken together, these results suggest that DRD1 methylation may constitute a biomarker of poor prognosis in NSCLC patients while other components of this pathway could be targeted to improve response to EGFR- and PD-L1-targeted therapies.

Marine phycotoxin levels in shellfish-14 years of data gathered along the Italian coast.

Along the Italian coasts, toxins of algal origin in wild and cultivated shellfish have been reported since the 1970s. In this study, we used data gathered by the Veterinary Public Health Institutes (IZS) and the Italian Environmental Health Protection Agencies (ARPA) from 2006 to 2019 to investigate toxicity events along the Italian coasts and relate them to the distribution of potentially toxic species. Among the detected toxins (OA and analogs, YTXs, PTXs, STXs, DAs, AZAs), OA and YTX were those most frequently reported. Levels exceeding regulatory limits in the case of OA (≤2,448 µg equivalent kg-1) were associated with high abundances of Dinophysis spp., and in the case of YTXs (≤22 mg equivalent kg-1) with blooms of Gonyaulax spinifera, Lingulodinium polyedra, and Protoceratium reticulatum. Seasonal blooms of Pseudo-nitzschia spp. occur all along the Italian coast, but DA has only occasionally been detected in shellfish at concentrations always below the regulatory limit (≤18 mg kg-1). Alexandrium spp. were recorded in several areas, although STXs (≤13,782 µg equivalent kg-1) rarely and only in few sites exceeded the regulatory limit in shellfish. Azadinium spp. have been sporadically recorded, and AZAs have been sometimes detected but always in low concentrations (≤7 µg equivalent kg-1). Among the emerging toxins, PLTX-like toxins (≤971 µg kg-1 OVTX-a) have often been detected mainly in wild mussels and sea urchins from rocky shores due to the presence of Ostreopsis cf. ovata. Overall, Italian coastal waters harbour a high number of potentially toxic species, with a few HAB hotspots mainly related to DSP toxins. Nevertheless, rare cases of intoxications have occurred so far, reflecting the whole Mediterranean Sea conditions.

Diverse eukaryotic phytoplankton from around the Marquesas Islands documented by combined microscopy and molecular techniques.

Oceanic phytoplankton serve as a base for the food webs within the largest planetary ecosystem. Despite this, surprisingly little is known about species composition, function and ecology of phytoplankton communities, especially for vast areas of the open ocean. In this study we focus on the marine phytoplankton microflora from the vicinity of the Marquesas Islands in the Southern Pacific Ocean collected during the Tara Oceans expedition. Multiple samples from four sites and two depths were studied in detail using light microscopy, scanning electron microscopy, and automated confocal laser scanning microscopy. In total 289 taxa were identified, with Dinophyceae and Bacillariophyceae contributing 60% and 32% of taxa, respectively, to phytoplankton community composition. Notwithstanding, a large number of cells could not be assigned to any known species. Coccolithophores and other flagellates together contributed less than 8% to the species list. Observed cell densities were generally low, but at sites of high autotrophic biomass, diatoms reached the highest cell densities (1.26 × 104 cells L-1). Overall, 18S rRNA metabarcode-based community compositions matched microscopy-based estimates, particularly for the main diatom taxa, indicating consistency and complementarity between different methods, while the wide range of microscopy-based methods permitted several unknown and poorly studied taxa to be revealed and identified.

A robust approach to estimate relative phytoplankton cell abundances from metagenomes.

Phytoplankton account for >45% of global primary production, and have an enormous impact on aquatic food webs and on the entire Earth System. Their members are found among prokaryotes (cyanobacteria) and multiple eukaryotic lineages containing chloroplasts. Genetic surveys of phytoplankton communities generally consist of PCR amplification of bacterial (16S), nuclear (18S) and/or chloroplastic (16S) rRNA marker genes from DNA extracted from environmental samples. However, our appreciation of phytoplankton abundance or biomass is limited by PCR-amplification biases, rRNA gene copy number variations across taxa, and the fact that rRNA genes do not provide insights into metabolic traits such as photosynthesis. Here, we targeted the photosynthetic gene psbO from metagenomes to circumvent these limitations: the method is PCR-free, and the gene is universally and exclusively present in photosynthetic prokaryotes and eukaryotes, mainly in one copy per genome. We applied and validated this new strategy with the size-fractionated marine samples collected by Tara Oceans, and showed improved correlations with flow cytometry and microscopy than when based on rRNA genes. Furthermore, we revealed unexpected features of the ecology of these ecosystems, such as the high abundance of picocyanobacterial aggregates and symbionts in the ocean, and the decrease in relative abundance of phototrophs towards the larger size classes of marine dinoflagellates. To facilitate the incorporation of psbO in molecular-based surveys, we compiled a curated database of >18,000 unique sequences. Overall, psbO appears to be a promising new gene marker for molecular-based evaluations of entire phytoplankton communities.

Extracellular matrix profiles determine risk and prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma.

BACKGROUND: Squamous cell carcinoma (SqCC) is a subtype of non-small cell lung cancer for which patient prognosis remains poor. The extracellular matrix (ECM) is critical in regulating cell behavior; however, its importance in tumor aggressiveness remains to be comprehensively characterized. METHODS: Multi-omics data of SqCC human tumor specimens was combined to characterize ECM features associated with initiation and recurrence. Penalized logistic regression was used to define a matrix risk signature for SqCC tumors and its performance across a panel of tumor types and in SqCC premalignant lesions was evaluated. Consensus clustering was used to define prognostic matreotypes for SqCC tumors. Matreotype-specific tumor biology was defined by integration of bulk RNAseq with scRNAseq data, cell type deconvolution, analysis of ligand-receptor interactions and enriched biological pathways, and through cross comparison of matreotype expression profiles with aging and idiopathic pulmonary fibrosis lung profiles. RESULTS: This analysis revealed subtype-specific ECM signatures associated with tumor initiation that were predictive of premalignant progression. We identified an ECM-enriched tumor subtype associated with the poorest prognosis. In silico analysis indicates that matrix remodeling programs differentially activate intracellular signaling in tumor and stromal cells to reinforce matrix remodeling associated with resistance and progression. The matrix subtype with the poorest prognosis resembles ECM remodeling in idiopathic pulmonary fibrosis and may represent a field of cancerization associated with elevated cancer risk. CONCLUSIONS: Collectively, this analysis defines matrix-driven features of poor prognosis to inform precision medicine prevention and treatment strategies towards improving SqCC patient outcome.

Phenological segregation suggests speciation by time in the planktonic diatom Pseudo-nitzschia allochrona sp. nov.

The processes leading to the emergence of new species are poorly understood in marine plankton, where weak physical barriers and homogeneous environmental conditions limit spatial and ecological segregation. Here, we combine molecular and ecological information from a long-term time series and propose Pseudo-nitzschia allochrona, a new cryptic planktonic diatom, as a possible case of speciation by temporal segregation. The new species differs in several genetic markers (18S, 28S and ITS rDNA fragments and rbcL) from its closest relatives, which are morphologically very similar or identical, and is reproductively isolated from its sibling species P. arenysensis. Data from a long-term plankton time series show P. allochrona invariably occurring in summer-autumn in the Gulf of Naples, where its closely related species P. arenysensis, P. delicatissima, and P. dolorosa are instead found in winter-spring. Temperature and nutrients are the main factors associated with the occurrence of P. allochrona, which could have evolved in sympatry by switching its phenology and occupying a new ecological niche. This case of possible speciation by time shows the relevance of combining ecological time series with molecular information to shed light on the eco-evolutionary dynamics of marine microorganisms.

LKB1 phosphorylation and deactivation in lung cancer by NNAL, a metabolite of tobacco-specific carcinogen, in an isomer-dependent manner.

LKB1 loss of function is one key oncogenic event in lung cancer. Clinical data suggest that LKB1 loss of function is associated with patients' smoking status. The responsible ingredients and molecular mechanisms in tobacco for LKB1 loss of function, however, are not defined. In this study, we reported that NNAL, a major metabolite of a tobacco-specific carcinogen NNK, induces LKB1 phosphorylation and its loss of function via the ß-AR/PKA signaling pathway in an isomer-dependent manner in human lung cancer cells. NNAL exposure also resulted in enhanced lung cancer cell migration and chemoresistance in an LKB1-dependent manner. A 120-day NNAL exposure in lung cancer cells, mimicking its chronic exposure among smokers, resulted in more prominent LKB1 phosphorylation, cell migration, and chemoresistance even in the absence of NNAL, indicating the long-lasting LKB1 loss of function although such an effect eventually disappeared after NNAL was removed for two months. These observations were confirmed in a lung cancer xenograft model. More importantly, human lung cancer tissues revealed elevated LKB1 phosphorylation in comparison to the paired normal lung tissues. These results suggest that LKB1 loss of function in human lung cancer could be extended to its phosphorylation, which may be mediated by NNAL from tobacco smoke in an isomer-dependent manner via the ß-AR/PKA signaling pathway.

Automated next-generation profiling of genomic alterations in human cancers.

The lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared for examination of 505 cancer-related genes. Independent analyses of clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, and PCR-based methods reveals a positive percent agreement of >97%. We observe high concordance with whole-exome sequencing for evaluation of tumor mutational burden for 307 solid tumors (Pearson r = 0.95) and comparison of the elio tissue complete microsatellite instability detection approach with an independent PCR assay for 223 samples displays a positive percent agreement of 99%. Finally, evaluation of amplifications and translocations against DNA- and RNA-based approaches exhibits >98% negative percent agreement and positive percent agreement of 86% and 82%, respectively. These methods provide an approach for pan-solid tumor comprehensive genomic profiling with high analytical performance.

Photoperiod-driven rhythms reveal multi-decadal stability of phytoplankton communities in a highly fluctuating coastal environment.

Phytoplankton play a pivotal role in global biogeochemical and trophic processes and provide essential ecosystem services. However, there is still no broad consensus on how and to what extent their community composition responds to environmental variability. Here, high-frequency oceanographic and biological data collected over more than 25 years in a coastal Mediterranean site are used to shed light on the temporal patterns of phytoplankton species and assemblages in their environmental context. Because of the proximity to the coast and due to large-scale variations, environmental conditions showed variability on the short and long-term scales. Nonetheless, an impressive regularity characterised the annual occurrence of phytoplankton species and their assemblages, which translated into their remarkable stability over decades. Photoperiod was the dominant factor related to community turnover and replacement, which points at a possible endogenous regulation of biological processes associated with species-specific phenological patterns, in analogy with terrestrial plants. These results highlight the considerable stability and resistance of phytoplankton communities in response to different environmental pressures, which contrast the view of these organisms as passively undergoing changes that occur at different temporal scales in their habitat, and show how, under certain conditions, biological processes may prevail over environmental forcing.

A comprehensive map of alternative polyadenylation in African American and European American lung cancer patients.

Deciphering the post-transcriptional mechanisms (PTM) regulating gene expression is critical to understand the dynamics underlying transcriptomic regulation in cancer. Alternative polyadenylation (APA)-regulation of mRNA 3'UTR length by alternating poly(A) site usage-is a key PTM mechanism whose comprehensive analysis in cancer remains an important open challenge. Here we use a method and analysis pipeline that sequences 3'end-enriched RNA directly to overcome the saturation limitation of traditional 5'-3' based sequencing. We comprehensively map the APA landscape in lung cancer in a cohort of 98 tumor/non-involved tissues derived from European American and African American patients. We identify a global shortening of 3'UTR transcripts in lung cancer, with notable functional implications on the expression of both coding and noncoding genes. We find that APA of non-coding RNA transcripts (long non-coding RNAs and microRNAs) is a recurrent event in lung cancer and discover that the selection of alternative polyA sites is a form of non-coding RNA expression control. Our results indicate that mRNA transcripts from EAs are two times more likely than AAs to undergo APA in lung cancer. Taken together, our findings comprehensively map and identify the important functional role of alternative polyadenylation in determining transcriptomic heterogeneity in lung cancer.

Toxic marine microalgae and noxious blooms in the Mediterranean Sea: A contribution to the Global HAB Status Report.

We review the spatial distribution of toxic marine microalgal species and the impacts of all types of harmful algal events (Harmful Algal Blooms, HABs) in the Mediterranean Sea (MS), including the Black Sea, the Sea of Marmara, coastal lagoons and transitional waters, based on two databases compiled in the Ocean Biogeographic Information System (OBIS). Eighty-four potentially toxic species have been detected in the MS (2,350 records), of which 16 described from these waters between 1860 and 2014 and a few suspected to have been introduced. More than half of these species (46) produce toxins that may affect human health, the remainders ichthyotoxic substances (29) or other types of toxins (9). Nevertheless, toxicity-related events are not frequent in the MS (308 records in 31 years), and mainly consist of impacts on aquaculture, caused by the dinoflagellates Dinophysis and Alexandrium, along with a few actual shellfish poisoning cases. Pseudo-nitzschia blooms are widespread, but domoic acid in shellfish rarely exceeds regulatory levels. Fish kills are probably less sporadic than reported, representing a problem at a few places along the southern MS coasts and in the Ebro River Delta. Since the last decade of the 20th century, blooms of the benthic dinoflagellates Ostreopsis cf. ovata have regularly occurred all along rocky shores of the MS, at times with human health problems caused by toxic aerosol. New records of Gambierdiscus and Fukuyoa, until now reported for the westernmost and easternmost MS coasts, raise concerns about the risk of ciguatera, a syndrome so far known only for subtropical and tropical areas. Recent discoveries are the dinoflagellates Vulcanodinium rugosum, responsible for the presence of pinnatoxins in French lagoons' shellfish, and the azaspiracid-producers Azadinium spp. Mucilages and discolorations have a major impact on tourism in summer. Reports of toxic species and HABs have apparently increased in the MS over the last half century, which is likely related to the increased awareness and monitoring operations rather than to an actual increase of these phenomena. Indeed, while the case of Ostreopsis appears as a sudden upsurge rather than a trend, no actual increase of toxic or noxious events has so far emerged in intensively studied areas, such as the French and Spanish coasts or the Adriatic Sea. Moreover, some cases of decrease are reported, e.g., for Alexandrium minutum blooms disappearing from the Harbour of Alexandria. Overall, main HAB risks derive from cases of massive development of microalgal biomass and consequent impacts of reduced coastal water quality on tourism, which represents the largest part of the marine economy along the MS coasts.

Global harmful algal bloom status reporting.

An extremely variegated picture of harmful algal bloom types and their socio-economic impacts at the regional and subregional scale emerges from the overviews presented in this special issue. The diversity of the HAB events parallels that of the causative species, which show different ranges and ecological characteristics, as well as highly variable responses to environmental changes. The intensity and frequency of specific blooms vary at regional and local scale, with increasing or decreasing trends and sudden occasional outbursts, but with no general uniform trend that can be discerned from that of increased observational efforts. In many cases intoxications and other adverse effects on human health are kept under control through increased monitoring activities, but impacts on human activities such as aquaculture, fishery, use of natural marine resources and tourism keep on posing economic activities at risk in many regions.

Perceived global increase in algal blooms is attributable to intensified monitoring and emerging bloom impacts.

Global trends in the occurrence, toxicity and risk posed by harmful algal blooms to natural systems, human health and coastal economies are poorly constrained, but are widely thought to be increasing due to climate change and nutrient pollution. Here, we conduct a statistical analysis on a global dataset extracted from the Harmful Algae Event Database and Ocean Biodiversity Information System for the period 1985-2018 to investigate temporal trends in the frequency and distribution of marine harmful algal blooms. We find no uniform global trend in the number of harmful algal events and their distribution over time, once data were adjusted for regional variations in monitoring effort. Varying and contrasting regional trends were driven by differences in bloom species, type and emergent impacts. Our findings suggest that intensified monitoring efforts associated with increased aquaculture production are responsible for the perceived increase in harmful algae events and that there is no empirical support for broad statements regarding increasing global trends. Instead, trends need to be considered regionally and at the species level.

Do plankton reflect the environmental quality status? The case of a post-industrial Mediterranean Bay.

While the effects of industrial contamination in coastal areas may persist for years in benthos communities, plankton should not show permanent impairments because of their high spatial dynamics, fast turnover times and pronounced seasonality. To test this hypothesis, in 2019 we conducted five surveys in the Bay of Pozzuoli (Gulf of Naples, Mediterranean Sea), in front of a dismissed steel factory and in the adjacent inshore coastal waters. High seasonal variability was observed for bacteria, phytoplankton and mesozooplankton, whereas plankton spatial gradients were relatively smooth during each survey. Plankton biomass and diversity did not reveal any effects of past industrial activities not even at the innermost stations of the Bay, which however showed some signals of present anthropogenic pressure. Hydrodynamic and morphological features likely play a prominent role in maintaining a relatively good status of the plankton of the Bay, which hints at the relevance of coastal circulation and meteorological dynamics to revitalize areas impacted by human activities.

Whole-Exome Profiling of NSCLC Among African Americans.

INTRODUCTION: Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States, especially among men. Although significant progress has been made profiling the genomic makeup of lung cancer in EAs, AAs continue to be underrepresented. Our objective was to chart the genome-wide landscape of somatic mutations in lung cancer tumors from AAs. METHODS: In this study, we used the whole-exome sequencing of 82 tumor and noninvolved tissue pairs from AAs. Patients were selected from an ongoing case-control study conducted by the National Cancer Institute and the University of Maryland. RESULTS: Among all samples, we identified 178 significantly mutated genes (p < 0.05), five of which passed the threshold for false discovery rate (p < 0.1). In lung adenocarcinoma (LUAD) tumors, mutation rates in STK11 (p = 0.05) and RB1 (p = 0.008) were significantly higher in AA LUAD tumors (25% and 13%, respectively) compared with The Cancer Genome Atlas EA samples (14% and 4%, respectively). In squamous cell carcinomas, mutation rates in STK11 (p = 0.002) were significantly higher among AA (8%) than EA tumors from The Cancer Genome Atlas (1%). Integrated somatic mutation data with CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts) data analysis revealed LUAD tumors from AAs carrying STK11 mutations have decreased interferon signaling. CONCLUSIONS: Although a considerable degree of the somatic mutation landscape is shared between EAs and AAs, discrete differences in mutation frequency in potentially important oncogenes and tumor suppressors exist. A better understanding of the molecular basis of lung cancer in AA patients and leveraging this information to guide clinical interventions may help reduce disparities.

Genome-enabled phylogenetic and functional reconstruction of an araphid pennate diatom Plagiostriata sp. CCMP470, previously assigned as a radial centric diatom, and its bacterial commensal.

Diatoms are an ecologically fundamental and highly diverse group of algae, dominating marine primary production in both open-water and coastal communities. The diatoms include both centric species, which may have radial or polar symmetry, and the pennates, which include raphid and araphid species and arose within the centric lineage. Here, we use combined microscopic and molecular information to reclassify a diatom strain CCMP470, previously annotated as a radial centric species related to Leptocylindrus danicus, as an araphid pennate species in the staurosiroid lineage, within the genus Plagiostriata. CCMP470 shares key ultrastructural features with Plagiostriata taxa, such as the presence of a sternum with parallel striae, and the presence of a highly reduced labiate process on its valve; and this evolutionary position is robustly supported by multigene phylogenetic analysis. We additionally present a draft genome of CCMP470, which is the first genome available for a staurosiroid lineage. 270 Pfams (19%) found in the CCMP470 genome are not known in other diatom genomes, which otherwise does not hold big novelties compared to genomes of non-staurosiroid diatoms. Notably, our DNA library contains the genome of a bacterium within the Rhodobacterales, an alpha-proteobacterial lineage known frequently to associate with algae. We demonstrate the presence of commensal alpha-proteobacterial sequences in other published algal genome and transcriptome datasets, which may indicate widespread and persistent co-occurrence.

Species detection and delineation in the marine planktonic diatoms Chaetoceros and Bacteriastrum through metabarcoding: making biological sense of haplotype diversity.

High-throughput sequencing (HTS) metabarcoding is commonly applied to assess phytoplankton diversity. Usually, haplotypes are grouped into operational taxonomic units (OTUs) through clustering, whereby the resulting number of OTUs depends on chosen similarity thresholds. We applied, instead, a phylogenetic approach to infer taxa among 18S rDNA V4-metabarcode haplotypes gathered from 48 time-series samples using the marine planktonic diatoms Chaetoceros and Bacteriastrum as test case. The 73 recovered taxa comprised both solitary haplotypes and polytomies, the latter composed each of a highly abundant, dominant haplotype and one to several minor, peripheral haplotypes. The solitary and dominant haplotypes usually matched reference sequences, enabling species assignation of taxa. We hypothesise that the super-abundance of reads in dominant haplotypes results from the homogenization effect of concerted evolution. Reads of populous peripheral haplotypes and dominant haplotypes show comparable distribution patterns over the sample dates, suggesting that they are part of the same population. Many taxa revealed marked seasonality, with closely related ones generally showing distinct periodicity, whereas others occur year-round. Phylogenies inferred from metabarcode haplotypes enable delineation of biologically meaningful taxa, whereas OTUs resulting from clustering algorithms often deviate markedly from such taxa.

Author Correction: Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Higher prevalence of homologous recombination deficiency in tumors from African Americans versus European Americans.

To improve our understanding of longstanding disparities in incidence and mortality in lung cancer across ancestry, we performed a systematic comparative analysis of molecular features in tumors from African Americans (AAs) and European Americans (EAs). We find that lung squamous cell carcinoma tumors from AAs exhibit higher genomic instability-the proportion of non-diploid genome-aggressive molecular features such as chromothripsis and higher homologous recombination deficiency (HRD). In The Cancer Genome Atlas, we demonstrate that high genomic instability, HRD and chromothripsis among tumors from AAs is found across many cancer types. The prevalence of germline HRD (that is, the total number of pathogenic variants in homologous recombination genes) is higher in tumors from AAs, suggesting that the somatic differences observed have genetic ancestry origins. We also identify AA-specific copy-number-based arm-, focal- and gene-level recurrent features in lung cancer, including higher frequencies of PTEN deletion and KRAS amplification. These results highlight the importance of including under-represented populations in genomics research.