The draft genome data for Cimex hemipterus obtained through Illumina HiSeq sequencing were presented. The raw genomic data was deposited in GenBank under BioProject (PRJNA722579) with the BioSample accession number SAMN18780126. Software, including FLASH, SPADES, and QUAST, were used to merge, assemble, and qualify the raw dataset. The assembled genome was available in the Figshare repository. The assembled genomic data was compared to C. hemipterus data obtained using 454 Roche shotgun sequencing (BioProject, PRJNA308532), downloaded from NCBI. The draft genome data from this work demonstrated larger data volumes and an updated assembly of the C. hemipterus genome with better scaffolding compared to genome data obtained from 454 Roche shotgun sequencing.

BACKGROUND: Racial and sex disparities in the incidence and outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) exist, yet potential genomic variations of iCCA based on race and sex that might be contributing to disparate outcomes have not been well studied.
METHODS: Data from the American Association for Cancer Research Project GENIE registry (version 15.0) were analyzed to assess genetic variations in iCCA. Adult patients (age >18 years) with histologically confirmed iCCA who underwent next-generation sequencing were included in the analytic cohort. Racial and sex variations in genomic profiling of iCCA were examined.
RESULTS: The study enrolled 1068 patients from 19 centers (White, 71.9%; Black, 5.1%; Asian, 8.4%, other, 14.6%). The male-to-female ratio was 1:1. The majority of the patients had primary tumors (73.7%), whereas 23.0% had metastatic disease sequenced. While IDH1 mutations occurred more frequently in White versus Black patients (20.8% vs. 5.6%; p = 0.021), FGFR2 mutations tended to be more common among Black versus White populations (27.8% vs. 16.1%; p = 0.08). Males were more likely to have TP53 mutations than females (24.3% vs. 18.2%, p = 0.016), whereas females more frequently had IDH1 (23.3% vs 16.0 %), FGFR2 (21.0% vs. 11.3%), and BAP1 (23.4% vs. 14.5%) mutations than males (all p < 0.05). Marked variations in the prevalence of other common genomic alterations in iCCA were noted across different races and sexes.
CONCLUSIONS: Distinct genomic variations exist in iCCA across race and sex. Differences in mutational profiles of iCCA patients highlight the importance of including a diverse patient population in iCCA clinical trials as well as the importance of recognizing different genetic drivers that may be targetable to treat distinct patient cohorts.

With the wide use of RNA sequencing technologies, the family of FET::CREB fusion mesenchymal neoplasms has expanded rapidly to include potentially aggressive neoplasms, not fitting any well established WHO entity. Recently, a group of intra-abdominal FET(EWSR1/FUS)::CREB(CREM/ATF1) fused unclassified neoplasms has been reported followed by recent recognition of an analogous extra-abdominal category of unclassified neoplasms carrying EWSR1::ATF1 fusions. We describe 9 additional tumors (5 extra-abdominal and 4 abdominal) carrying an EWSR1::CREM (n = 8) and FUS::CREM (n = 1) fusion. Patients were 7 females and 2 males aged 10 to 75 years (median, 34). Extra-abdominal tumors originated in the head and neck (2 sinonasal, 1 orbital) and soft tissues (1 gluteal, 1 inguinal). Abdominal tumors involved stomach (2), mesentery (1), and kidney (1). Tumor size ranged from 3.5 to 11 cm (median, 6). Treatment was radical surgery with (5) or without (2) neo/adjuvant radio/chemotherapy. Extended follow-up of 5 patients (21-52 months; median, 24) showed an aggressive course in two (40%); one died of disseminated metastases 52 months after several intensified chemotherapy regimens, and one was alive with progressive abdominal disease at 21 months. The immunophenotype of the two subcohorts was significantly overlapping with variable expression of EMA (7 of 8), keratin AE1/AE3 (5 of 9), CD99 (4 of 7), MUC4 (2 of 8), ALK (3 of 8), synaptophysin (3 of 9), chromogranin (1 of 8), CD34 (3 of 6), CD30 (1 of 6), PAX8 (1 of 7), and inhibin (1 of 7), but no reactivity with desmin (0 of 8), S100 (0 of 8), and SOX10 (0 of 8). This series further solidifies the notion that FET::CREB fusions are not limited to the triad of angiomatoid fibrous histiocytoma, clear cell sarcoma, and malignant gastrointestinal neuroectodermal tumor, but characterize an emerging family of potentially aggressive neoplasms occurring at both intra- and extra-abdominal sites. These tumors underscore the promiscuity of the FET::CREB fusions and highlight the pivotal role of phenotype-oriented classification of these neoplasms that share the same genotype, still featuring significant biological and behavioral distinctness.

Angiosarcomas of the kidney and adrenal gland are rare, highly aggressive vascular neoplasms. Their genomic profile has not been systematically studied to date. We report the clinicopathologic and molecular features of six angiosarcomas centered in the kidney/adrenal gland. All patients were male adults, ranging from 58 to 77 years of age. Tumor sizes ranged from 2.5 to 22.5 cm. Half of the cases demonstrated hot spot mutations in the KDR gene, while one-third demonstrated mutations in the PIK3CA gene; both of these gene alterations being previously described, preferentially in breast angiosarcomas. In addition, two cases each demonstrated BRIP1 gene amplification, CTNNB1 and ETV6 mutations, which have not been previously reported in angiosarcoma. Notably, molecular studies were critical in establishing the correct diagnoses in three cases: one was an epithelioid angiosarcoma originally misdiagnosed as metastatic adenocarcinoma to the adrenal gland, the second was a vasoformative angiosarcoma that mimicked hemangioma, and the third was a collision tumor between a high-grade angiosarcoma and a chromophobe renal cell carcinoma which was originally diagnosed as a sarcomatoid renal cell carcinoma. In summary, angiosarcomas of the kidney and adrenal gland have a high frequency of recurrent genetic alterations, some of them being shared with other angiosarcoma subtypes, while other appear to be novel. In particular, activating hot spot KDR and PIK3CA mutations represent potential therapeutic targets for these highly aggressive cancers.

Sporotrichosis is a common chronic fungal infection and the clinical manifestations are often untypical. Diagnosis of sporotrichosis relies conventionally on fungal culture, histopathological examination, and species identification by molecular test. We reported that a 70-year-old man presented with a cutaneous lesion on the back of his right hand (present for 6 months). The cutaneous bacterial infection was diagnosed at a local hospital and the lesion had not improved. Physical examination revealed an infiltrative reddish plaque with purulent secretion and crusts. Histopathological examination revealed scattered round yeast cells in the dermis. Fungal culture revealed multiple, velvety, brown colonies on Sabouraud dextrose agar (SDA). Sporothrix globosa was identified by PCR-sequencing and next generation sequencing (NGS) method. Finally, a case of sporotrichosis caused by Sporothrix globosa was diagnosed by histopathological examination, mycological examination, and molecular identification. The patient was treated with oral itraconazole 400 mg/day for 2 months. The lesion was dramatically ameliorated.

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.

A pilot study was performed using two different DNA technology platforms conducted by two laboratories to analyze DNA extracted from 83-year-old, human male skeletal remains from 16 individuals, of which there are no other viable means to identify these war victims. The workflow of the more recent developed ForenSeq Kintelligence Kit and next generation sequencing was compared to that of the standard capillary electrophoresis - short tandem repeat (STR) method (Power Plex ESX17 and Y23 Systems). The findings indicate that greater amount of useful genetic data can be gained with the Kintelligence system across the range of samples under study and particularly for samples in which partial or no STR profiles are obtained. SNP data are more likely to be obtained from degraded samples, like the ones analyzed in this study. Moreover, high volume SNP data are suitable for long distance kinship associations and genetic genealogy databases to develop more investigative leads for future kinship and missing persons cases, a process not feasible by STR typing.

In this study, total RNA high-throughput sequencing (HTS) of a single symptomatic Phytolacca americana plant enabled the obtention of a nearly complete genome of two new isolates of turnip yellows virus (TuYV), named TuYV-ITA1 and TuYV-ITA2, and revealed a mixed infection with a new variant of citrus exocortis viroid (CEVd), named CEVd-ITA1. The TuYV-ITA2 isolate diverged from the known virus isolates of TuYV and showed variability in the P0 and P5 readthrough domain. Recombination analysis revealed its recombinant nature between TuYV and an unidentified polerovirus. The putative recombination event was identified in the P5 readthrough domain of the TuYMV-ITA2 isolate. Our results thus represent the first report of TuYV in Italy and some molecular evidence for the possible natural co-existence of TuYV and CEVd in a new natural host for both infectious entities. This study is adding further knowledge about the role of weed plants as virus reservoirs, and thus additional biological and impact studies would be desirable to determine in particular the role of P. americana in the spread of TuYV and if this virus should be considered a new threat for the susceptible Italian crops.

There is discussion of expanding newborn screening (NBS) through the use of genomic sequence data; yet, challenges remain in the interpretation of DNA variants. Population-level DNA variant databases are available, and it is possible to estimate the number of newborns who would be flagged as having a risk for a genetic disease (including rare variants of unknown significance, VUS) via next-generation sequencing (NGS) positive. Estimates of the number of newborns screened as NGS positive for monogenic recessive diseases were obtained by analysis of the Genome Aggregation Database (gnomAD). For a collection of diseases for which there is interest in NBS, we provided 2 estimates for the expected number of newborns screened as NGS positive. For a set of lysosomal storage diseases, we estimated that 100 to approximately 600 NGS screen positives would be found per disease per year in a large NBS laboratory (California), and this figure may be expected to rise to a limit of about 1000 if we account for the fact that gnomAD does not contain all worldwide variants. The number of positives would drop 2.5- to 10-fold if the 10 VUS with highest allele frequency were biochemically annotated as benign. It is proposed that a second-tier biochemical assay using the same dried blood spot could be carried out as a filter and as part of NBS to reduce the number of high-risk NGS positive newborns to a manageable number.

Two novel Class I HLA-B alleles HLA-B*13:194 and HLA-B*15:694 are described.