Non-Mitochondrial Aconitase-2 Mediates the Transcription of Nuclear-Encoded Electron Transport Chain Genes in Fission Yeast.

Aconitase-2 (Aco2) is present in the mitochondria, cytosol, and nucleus of fission yeast. To explore its function beyond the well-known role in the mitochondrial tricarboxylic acid (TCA) cycle, we conducted genome-wide profiling using the aco2ΔNLS mutant, which lacks a nuclear localization signal (NLS). The RNA sequencing (RNA-seq) data showed a general downregulation of electron transport chain (ETC) genes in the aco2ΔNLS mutant, except for those in the complex II, leading to a growth defect in respiratory-prone media. Complementation analysis with non-catalytic Aco2 [aco2ΔNLS + aco2(3CS)], where three cysteines were substituted with serine, restored normal growth and typical ETC gene expression. This suggests that Aco2's catalytic activity is not essential for its role in ETC gene regulation. Our mRNA decay assay indicated that the decrease in ETC gene expression was due to transcriptional regulation rather than changes in mRNA stability. Additionally, we investigated the Php complex's role in ETC gene regulation and found that ETC genes, except those within complex II, were downregulated in php3Δ and php5Δ strains, similar to the aco2ΔNLS mutant. These findings highlight a novel role for nuclear aconitase in ETC gene regulation and suggest a potential connection between the Php complex and Aco2.

Prophylactic efficacy of baicalin and carvacrol against Salmonella Typhimurium biofilm on food and food contact surfaces.

This study examines the antimicrobial and antibiofilm effectiveness of baicalin and carvacrol against Salmonella enterica ser. Typhimurium on food contact surfaces and chicken meat. The minimum inhibitory concentrations (MIC) for baicalin and carvacrol were found to be 100 µg/mL and 200 µg/mL, respectively, which aligns with findings from previous studies. The compounds exhibited a concentration-dependent decrease in microbial populations and biofilm formation. When used together, they displayed a remarkable synergistic effect, greatly augmenting their antibacterial activity. The assessment of food quality demonstrated that these treatments have no negative impact on the sensory characteristics of chicken meat. The impact of the structure on biofilms was observed through the use of Field Emission Scanning Electron Microscopy (FE-SEM) and Confocal Laser Scanning Microscopy (CLSM), revealing disrupted biofilm architectures and decreased cell viability. Crucially, RT-PCR analysis revealed a marked downregulation of quorum sensing (luxS), virulence (hilA), and stress response (rpoS) genes, highlighting the multifaceted antimicrobial mechanism of action. This gene-specific suppression suggests a targeted disruption of bacterial communication and virulence pathways, offering insight into the comprehensive antibiofilm strategy. This provides further insight into the molecular mechanisms that contribute to their antibiofilm effects.

Isolation and characterization of multidrug-resistant Salmonella-specific bacteriophages and their antibacterial efficiency in chicken breast.

The use of phages as biocontrol agents against antibiotic-resistant strains of Salmonella spp. is gaining attention. This study aimed to isolate lytic bacteriophages specific for multidrug-resistant Salmonella enterica serovars Typhimurium; it also evaluated the bactericidal effect of isolated phages (STP-1, STP-2, STP-3, and STP-4) from sewage sample against S. Typhimurium as host strains. Moreover, a current study evaluated the efficacy of a bacteriophage cocktail against S. Typhimurium cocktail in chicken breast meat. The 4 phages were classified under the Caudoviricetes class by morphology characterization. On host range testing, they exhibited lytic activities against S. Typhimurium, S. Enteritidis, and S. Thompson. In the stability test, the phages exhibited resistance to heat (above 70°C for 1 h) and pH (strongly alkaline for 24 h). Additionally, the phages had comparable adsorption rates (approximately 80% adsorption in under 5 min). Additionally, the latent periods ranged from 30 to 50 min, with respective burst sizes of 31, 218, 197, and 218 PFU/CFU. In vitro, bacterial challenge demonstrated that at a multiplicity of infection (MOI) of 10, each phage consistently inhibited S. Typhimurium growth at 37°C for 24 h. In the food test, the phage cocktail (MOI = 1,000) reduced S. Typhimurium in artificially contaminated chicken breast meat stored at 4°C by 0.9 and 1.2 log CFU/g after 1 and 7 d, respectively. The results point toward a promising avenue for addressing the challenge of multidrug-resistant S. Typhimurium in the food industry through the use of recently discovered phages. Notably, the exploration of phage cocktails holds significant potential for combating S. Typhimurium in chicken breast products in the times ahead.

Diagnostic proficiency test using digital cytopathology and comparative assessment of whole slide images of cytologic samples for quality assurance program in Korea.

BACKGROUND: The Korean Society for Cytopathology introduced a digital proficiency test (PT) in 2021. However, many doubtful opinions remain on whether digitally scanned images can satisfactorily present subtle differences in the nuclear features and chromatin patterns of cytological samples. METHODS: We prepared 30 whole-slide images (WSIs) from the conventional PT archive by a selection process for digital PT. Digital and conventional PT were performed in parallel for volunteer institutes, and the results were compared using feedback. To assess the quality of cytological assessment WSIs, 12 slides were collected and scanned using five different scanners, with four cytopathologists evaluating image quality through a questionnaire. RESULTS: Among the 215 institutes, 108 and 107 participated in glass and digital PT, respectively. No significant difference was noted in category C (major discordance), although the number of discordant cases was slightly higher in the digital PT group. Leica, 3DHistech Pannoramic 250 Flash, and Hamamatsu NanoZoomer 360 systems showed comparable results in terms of image quality, feature presentation, and error rates for most cytological samples. Overall satisfaction was observed with the general convenience and image quality of digital PT. CONCLUSIONS: As three-dimensional clusters are common and nuclear/chromatin features are critical for cytological interpretation, careful selection of scanners and optimal conditions are mandatory for the successful establishment of digital quality assurance programs in cytology.

Functional viromic screens uncover regulatory RNA elements.

The number of sequenced viral genomes has surged recently, presenting an opportunity to understand viral diversity and uncover unknown regulatory mechanisms. Here, we conducted a screening of 30,367 viral segments from 143 species representing 96 genera and 37 families. Using a library of viral segments in 3' UTR, we identified hundreds of elements impacting RNA abundance, translation, and nucleocytoplasmic distribution. To illustrate the power of this approach, we investigated K5, an element conserved in kobuviruses, and found its potent ability to enhance mRNA stability and translation in various contexts, including adeno-associated viral vectors and synthetic mRNAs. Moreover, we identified a previously uncharacterized protein, ZCCHC2, as a critical host factor for K5. ZCCHC2 recruits the terminal nucleotidyl transferase TENT4 to elongate poly(A) tails with mixed sequences, delaying deadenylation. This study provides a unique resource for virus and RNA research and highlights the potential of the virosphere for biological discoveries.

Prolapsed Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Case Report and Review of Radiologic Findings.

INTRODUCTION: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor that arises in the myometrium of the uterus. It is regarded as an intermediate malignant tumor according to the recent World Health Organization classification. Few studies have reported the radiologic findings of STUMP, and the differentiation of STUMP from leiomyoma remains controversial. CASE DESCRIPTION: A 42-year-old nulliparous female presented at our institution with massive vaginal bleeding. Radiological studies, including ultrasonography, computed tomography (CT), and magnetic resonance imaging, revealed an oval-shaped mass with well-defined margins in the uterus protruding into the vagina. The patient underwent a total abdominal hysterectomy, and the final pathology was confirmed as STUMP. CONCLUSION: Distinguishing STUMP from leiomyomas based solely on radiological findings can be challenging. However, if the uterine mass appears as a single mass lacking acoustic shadowing on ultrasound and demonstrates diffusion restriction with high T2 signal intensity on magnetic resonance imaging, consideration of STUMP may be necessary for proper patient management, given the poor prognosis associated with this tumor.

A Patient of Venous Hemangioma of the Inferior Turbinate.

Sinonasal hemangiomas are relatively rare among the hemangiomas that occur from the head and neck parts. According to their histopathologic findings, they are classified as capillary, cavernous, or venous type. Some cases of capillary or cavernous hemangioma that occur from the inferior turbinate have been reported. However, there was no reported case of venous hemangioma arising from the inferior turbinate. We present a case of 67-year-old male who has venous hemangioma of the left inferior turbinate whose initial symptoms were watery rhinorrhea and postnasal drip. With this study, although uncommon, venous hemangioma should be considered as a differential diagnosis in patient with mass lesion of the inferior turbinate.

Coexpression of lymphocyte-activation gene 3 and programmed death ligand-1 in tumor infiltrating immune cells predicts worse outcome in renal cell carcinoma.

OBJECTIVES: Lymphocyte-activation gene 3 (LAG-3) represents a potential immune checkpoint target for cancer treatment. We investigated LAG-3 expression and its prognostic value in patients with surgically treated clear cell renal cell carcinoma (RCC) and correlated LAG-3 expression with programmed cell death ligand 1(PD-L1). METHODS: We evaluated LAG-3 and PD-L1 expression using immunohistochemistry on tissue microarrays incorporating 134 primary excision specimens of clear cell RCC (ccRCC). The patients were analyzed as two groups: the whole cohort and those with metastatic RCC (mRCC). The cancer genome atlas (TCGA) data analysis of LAG-3 was done through UALCAN web servers. RESULTS: Using the UALCAN cancer transcriptional data analysis, we found that LAG-3 was overexpressed in ccRCC. LAG-3 expression was significantly correlated with PD-L1 expression in the whole cohort and in the mRCC group (all, p < 0.05). Both LAG-3⁺ RCC and PD-L1⁺ RCC presented with a higher TNM stage and higher Fuhrman nuclear grade (all, p < 0.05). PD-L1⁺/LAG-3⁺ RCC and PD-L1⁻/LAG-3⁺ RCC showed poorer cancer-specific survival (CSS) than PD-L1⁻/LAG-3⁻ RCC (all, p = 0.01). Similarly, PD-L1⁺/LAG-3⁺ mRCC and PD-L1⁻/LAG-3⁺ mRCC showed poorer CSS than PD-L1⁻/LAG-3⁻ mRCC (all, p < 0.05). Multivariate analysis showed that PD-L1⁺/LAG-3⁺ mRCC (hazard ratio: 3.19; 95% CI: 0.77-13.67; p = 0.033) was a predictor of poor CSS. CONCLUSION: Both LAG-3⁺ and PD-L1⁺ RCC have adverse pathological features, and their coexpression predicts worse clinical outcomes. Our findings suggest LAG-3 blockade in combination with programmed cell death 1/PD-L1 blockade as a potential therapeutic approach for RCC.

Progressive Multifocal Leukoencephalopathy With Hyper-IgM Syndrome in a 6-Year-Old Boy.

Hyper-immunoglobulin (Ig) M syndrome is a congenital immunodeficiency disorder characterized by increased serum IgM with low serum IgG, IgA, and IgE. We report the case of a 6-year-old boy with hyper-IgM syndrome as an underlying disease who showed progressive multifocal leukoencephalopathy findings on brain magnetic resonance imaging after visiting the hospital due to left upper extremity muscle weakness, gait disturbance, and speech impairment. At the time of hospitalization, he was treated with steroids and intravenous immunoglobulin, and his condition improved somewhat, but 6 months later, he visited the hospital with rapid deterioration.

Non-mitochondrial aconitase regulates the expression of iron-uptake genes by controlling the RNA turnover process in fission yeast.

Aconitase, a highly conserved protein across all domains of life, functions in converting citrate to isocitrate in the tricarboxylic acid cycle. Cytosolic aconitase is also known to act as an iron regulatory protein in mammals, binding to the RNA hairpin structures known as iron-responsive elements within the untranslated regions of specific RNAs. Aconitase-2 (Aco2) in fission yeast is a fusion protein consisting of an aconitase and a mitochondrial ribosomal protein, bL21, residing not only in mitochondria but also in cytosol and the nucleus. To investigate the role of Aco2 in the nucleus and cytoplasm of fission yeast, we analyzed the transcriptome of aco2ΔN mutant that is deleted of nuclear localization signal (NLS). RNA sequencing revealed that the aco2ΔN mutation caused increase in mRNAs encoding iron uptake transporters, such as Str1, Str3, and Shu1. The half-lives of mRNAs for these genes were found to be significantly longer in the aco2ΔN mutant than the wild-type strain, suggesting the role of Aco2 in mRNA turnover. The three conserved cysteines required for the catalytic activity of aconitase were not necessary for this role. The UV cross-linking RNA immunoprecipitation analysis revealed that Aco2 directly bound to the mRNAs of iron uptake transporters. Aco2-mediated degradation of iron-uptake mRNAs appears to utilize exoribonuclease pathway that involves Rrp6 as evidenced by genetic interactions. These results reveal a novel role of non-mitochondrial aconitase protein in the mRNA turnover in fission yeast to fine-tune iron homeostasis, independent of regulation by transcriptional repressor Fep1.

Pancreatic Acinar Cell Cystadenoma Mimicking Pancreatic Serous Cystadenoma.

Acinar cell cystadenoma, also known as an acinar cystic transformation of the pancreas, is an exceedingly rare but benign pancreatic lesion. A 51-year-old woman was transferred to Inje University Busan Paik Hospital because of an 8 cm-sized calcified, multiseptated, and multilocular cystic mass in the pancreatic tail observed during abdominal CT performed at another hospital. The patient did not complain of abdominal pain or other symptoms, and her laboratory findings were normal. MRI showed that the cyst was not connected to the main pancreatic duct. A pancreatic serous cystadenoma was suspected, and a laparoscopic distal pancreatectomy was performed. The resected mass was composed of variable sized multilocular cysts with incomplete septa and focally lined by epithelium with acinar differentiation. The patient was diagnosed with acinar cell cystadenoma and is currently being followed up regularly. No complications or recurrences have been observed.

The application of bacteriophage to control Cronobacter sakazakii planktonic and biofilm growth in infant formula milk.

The goal was to identify the biofilm-forming ability of Cronobacter sakazakii on surfaces of stainless steel (SS) and silicone rubber (SR) in contact with infant formula milk. Two representative bacteriophages (PBES04 and PBES19) were used to control the growth of C. sakazakii as well as its biofilm forming ability on either SS or SR surfaces. Bacterial growth was confirmed at 20 °C when PBES04 and PBES19 were used, whereas C. sakazakii was not normally detected in infant formula milk treated with both bacteriophages for 6 h. In an additional biofilm reduction experiment, the biofilm on SS or SR surfaces were reduced by 3.07 and 1.92 log CFU cm-2, respectively after PBES04 treatment, and 3.06 and 2.14 log CFU cm-2, respectively, after PBES19 treatment. These results demonstrate that bacteriophages can be effective in inactivating C. sakazakii in biofilms which could potentially increase food safety in commercial facilities.

Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.

Retropharyngeal chordoma extending to the spinal cord, mimicking a neurogenic tumor: a case report and literature review.

Chordomas are rare, locally aggressive bone malignancies with poor prognoses. However, those with minimal or no bone involvement are more easily resectable because of their well-delineated margins and thus have better prognoses. Such extraosseous chordomas of the spine are localized both intradurally and extradurally. Only a few case reports have focused on extraosseous, extradural spinal chordomas. Radiologically, this type of chordoma has a dumbbell shape; however, dumbbell-shaped spinal tumors are traditionally thought to be neurogenic tumors (i.e., schwannomas or neurofibromas). We herein report a unique case involving a woman with a dumbbell-shaped extraosseous chordoma protruding predominantly into the retropharyngeal space. A 44-year-old woman presented for evaluation of a left submandibular mass. A T2-hyperintense, gadolinium-enhancing mass was found in her cervical spinal canal, protruding through the C2/3 neural foramen into the retropharyngeal space with minimal vertebral involvement. The initial diagnosis was a neurogenic tumor, most likely a schwannoma. After subtotal removal, the pathologic diagnosis was a chordoma. Because chordomas and schwannomas have significantly different prognoses, caution is warranted when a dumbbell-shaped tumor is identified in the spine with minimal or no vertebral deterioration on radiology. This report also provides the first thorough review of extraosseous dumbbell-shaped intraspinal-extraspinal chordomas.

Correlations between the Clinical and Ultrasonographic Parameters of Congenital Muscular Torticollis without a Sternocleidomastoid Mass.

OBJECTIVE: To determine whether ultrasonography at initial presentation can help assess the clinical severity of congenital muscular torticollis (CMT) in infants without a sternocleidomastoid muscle (SCM) mass. MATERIALS AND METHODS: This retrospective study included 71 infants aged less than 12 months (4.1 ± 2.3 months) with non-mass CMT. The clinical severity was divided into three grades (groups 1-3) based on the degree of lateral head bending or cervical rotation. The difference (SCM-D) and ratio (SCM-R) between the maximal thickness of the affected and non-affected SCMs were obtained using transverse and longitudinal ultrasonography. The sonographic echotexture and echogenicity of the involved SCM were reviewed. RESULTS: A significant difference was observed in the SCM-D (0.42 ± 0.30 mm in group 1; 0.74 ± 0.50 mm in group 2; 1.14 ± 0.85 mm in group 3; p = 0.002) and SCM-R (1.069 ± 0.067 in group 1; 1.129 ± 0.087 in group 2; 1.204 ± 0.150 in group 3; p = 0.001) among the groups when measured along the longitudinal but not along the transverse ultrasonography plane. The areas under the curves of the SCM-R and SCM-D measured by longitudinal ultrasonography were 0.731 (p < 0.001) and 0.731 (p < 0.001) for group 1 versus groups 2-3. The proportions of heterogeneous echotexture or hyperechogenicity in the involved SCM did not differ significantly among the three clinical groups (all p > 0.05). CONCLUSION: Ultrasonography can aid in assessing the clinical severity of CMT in infants without an SCM mass at the time of initial diagnosis. The SCM-R and SCM-D helped grade the clinical severity when obtained by longitudinal scan.

Comparison of Ultrasonography Features and K-TIRADS for Isthmic and Lobar Papillary Thyroid Carcinomas: A Single-Center Study.

Objective: This study aimed to compare ultrasonography (US) features and the Korean-Thyroid Imaging Reporting and Data System (K-TIRADS) categories for diagnosing isthmic and lobar papillary thyroid carcinomas (PTC). Methods: From January 2009 to December 2012, 163 patients who underwent thyroid surgery and were confirmed with a post-operative histopathological diagnosis of isthmic PTC were retrospectively included. Fifty-nine patients were excluded because their tumor size was <0.5 cm or because of other reasons. The control group comprised of 145 patients who underwent thyroid surgery from January to April 2013 for a classic type of PTC, with the largest diameter being ≥ 0.5 cm and located in the thyroid lobe. A single radiologist retrospectively reviewed the US features and K-TIRADS categories of each nodule using a picture archiving and communication system. Results: Among 104 patients with isthmic PTC, 95 and 9 had primary and secondary cancers, respectively. On the other hand, all 145 patients with lobar PTC had primary cancers. Isthmic PTC showed a lower prevalence of non-parallel orientation than lobar PTC (23.1 and 71%). Nodule orientation was the only US feature statistically different between the two groups (p < 0.0001). However, there was no significant difference in patient age, sex, nodule size, composition, echogenicity, microcalcification, spiculated/microlobulated margin, and K-TIRADS category between the two groups (p > 0.05). Conclusions: K-TIRADS may be useful in the diagnosis of both isthmic and lobar PTC.

Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing.

TENT4 enzymes generate 'mixed tails' of diverse nucleotides at 3' ends of RNAs via nontemplated nucleotide addition to protect messenger RNAs from deadenylation. Here we discover extensive mixed tailing in transcripts of hepatitis B virus (HBV) and human cytomegalovirus (HCMV), generated via a similar mechanism exploiting the TENT4-ZCCHC14 complex. TAIL-seq on HBV and HCMV RNAs revealed that TENT4A and TENT4B are responsible for mixed tailing and protection of viral poly(A) tails. We find that the HBV post-transcriptional regulatory element (PRE), specifically the CNGGN-type pentaloop, is critical for TENT4-dependent regulation. HCMV uses a similar pentaloop, an interesting example of convergent evolution. This pentaloop is recognized by the sterile alpha motif domain-containing ZCCHC14 protein, which in turn recruits TENT4. Overall, our study reveals the mechanism of action of PRE, which has been widely used to enhance gene expression, and identifies the TENT4-ZCCHC14 complex as a potential target for antiviral therapeutics.

Prevalence and Features of Thyroglossal Duct Cyst on Ultrasonography, According to Radioactive Iodine Therapy: A Single-Center Study.

Objective: The relationship between radioactive iodine therapy (RIT) and prevalence of thyroglossal duct cysts (TGDC) on ultrasonography (US) has not been reported. We assessed the prevalence and US features of TGDC according to RIT. Methods: From July 2017 to June 2018, 3,146 subjects underwent thyroid or neck US at our center. The presence or absence of TGDCs was prospectively investigated based on real-time US examination. Among the 3,146 subjects, 261 subjects were excluded because of <18 years of age, unclear information of RIT, or the presence of a radiation therapy history to the neck. Eventually, 2,885 subjects were included in this study. Results: Of the 2,885 subjects finally included, 126 (4.4%) showed a TGDC on US. Those with RIT history showed a higher prevalence of TGDCs than those without (no statistical difference, p = 0.062). In 697 male subjects, there were statistical differences in type of surgery, RIT history, and session number of RIT between those with or without TGDCs (p < 0.0001). In 126 subjects with TGDCs, only sex showed a significant difference between those with or without RIT history (p = 0.015). However, there were no significant differences in the location, size, and shape of TGDCs (p > 0.05). The common US features of TGDC were suprahyoid location, ~1 centimeter, and flat-to-ovoid or round shape. Conclusions: RIT may increase the prevalence of TGDCs, particularly in men.

Characterization of Salmonella spp.-specific bacteriophages and their biocontrol application in chicken breast meat.

Chicken breast meat is considered as the main source of Salmonella infection in humans. The aim of this study was to isolate lytic bacteriophages specific for Salmonella enterica serovars Enteritidis and examine their efficacy in a cocktail for the biocontrol of Salmonella spp. in raw chicken breast meat. Four lytic phages belonging to the Myoviridae and Siphoviridae families were isolated from a river proximate to a duck farm. They exhibited broad lytic activities against 11 strains of S. Enteritidis, 11 strains of S. Typhimurium, and one each of S. Paratyphi A, S. San Diego, and S. Typhi. The phages were determined to be stable, exhibited similar degrees of resistance to heat and pH, and had latent periods ranging from 5 to 30 min. In addition, the phage particles were 100% adsorbed within 18 to 40 min. Viable cell counts of bacteria were significantly reduced in raw chicken breast samples (P < 0.05) when treated with a cocktail of all four bacteriophages at 4 °C for 7 days (multiplicities of infection were from 104 to 106 ). These results indicate the potential efficacy of the bacteriophage cocktail as a biological agent against S. Enteritidis in raw chicken breast meat. PRACTICAL APPLICATION: Our findings demonstrate that the phages could be effective in reducing the viability of Salmonella spp. bacteria in chicken breast meat. Therefore, the phage cocktail is a potential bactericidal agent for the biocontrol of Salmonella spp. in raw chicken breast meat and could be used use in various poultry industries in the future.

Genomic Landscape of Young-Onset Bladder Cancer and Its Prognostic Implications on Adult Bladder Cancer.

Due to the rare occurrence of young-onset bladder cancer (YBC), its genomic characteristics remain largely unknown. Twenty-nine biopsy-proven YBC cases were collected using a nation-wide search for bladder cancer diagnosed at 20 years or younger. Whole exome sequencing and RNA sequencing were carried out in 21 and 11 cases, respectively, and compared with those of adult bladder cancer (ABC) cases obtained from public databases. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had a low mutation burden and less complex copy number alterations. All cases harbored putative driver mutations. Mutations were most commonly found in HRAS (10 cases), with a preference for exon 5. FGFR3 gene fusions were noted with various partner genes (7 cases). The alterations on HRAS and FGFR3 occurred in a mutually exclusive manner. Others included KRAS mutations (2 cases), chromosomes 4p and 10q arm-level deletions (1 case), and ERCC2 mutation (1 case). There were no point mutations in TP53 and FGFR3. The gene expression profiles of YBC were similar to those of the ABC group with good prognosis. None of the YBCs and ABCs with YBC-like mutations showed progression to muscle-invasive tumors. Our results suggest that bladder cancer with YBC-like mutations represents an indolent bladder tumor, regardless of age.