A cascade nanosystem with "Triple-Linkage" effect for enhanced photothermal and activatable metal ion therapy for hepatocellular carcinoma.

Due to the limitations of single-model tumor therapeutic strategies, multimodal combination therapy have become a more favorable option to enhance efficacy by compensating for its deficiencies. However, in nanomaterial-based multimodal therapeutics for tumors, exploiting synergistic interactions and cascade relationships of materials to achieve more effective treatments is still a great challenge. Based on this, we constructed a nanoplatform with a "triple-linkage" effect by cleverly integrating polydopamine (PDA), silver nanoparticles (AgNPs), and glucose oxidase (GOx) to realize enhanced photothermal therapy (PTT) and activatable metal ion therapy (MIT) for hepatocellular carcinoma (HCC) treatment. First, the non-radiative conversion of PDA under light conditions was enhanced by AgNPs, which directly enhanced the photothermal conversion efficiency of PDA. In addition, GOx reduced the synthesis of cellular heat shock proteins by interfering with cellular energy metabolism, thereby enhancing cellular sensitivity to PTT. On the other hand, H2O2, a by-product of GOx-catalyzed glucose, could be used as an activation source to activate non-toxic AgNPs to release cytotoxic Ag+, achieving activatable Ag+-mediated MIT. In conclusion, this nanosystem achieved efficient PTT and MIT for HCC by exploiting the cascade effect among PDA, AgNPs, and GOx, providing a novel idea for the design of multimodal tumor therapeutic systems with cascade regulation.

Exosomal lncCRLA is predictive for the evolvement and development of lung adenocarcinoma.

Lung adenocarcinoma, the most common histological subtype of non-small cell lung cancer, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Our team uncovers that lncRNA related to chemotherapy resistance in lung adenocarcinoma (lncCRLA) is preferentially expressed in lung adenocarcinoma cells with the mesenchymal phenotype. lncCRLA can not enhance chemotherapy resistance in lung adenocarcinoma due to its binding to RIPK1 in exosomes, which is released into intercellular media and transferred by exosomes from mesenchymal-like to epithelial-like cells. However, plasmatic lncCRLA corresponding to tissue lncCRLA functions as a preferred biomarker to reflect the response to chemotherapy and disease progression of lung adenocarcinoma. Through single-cell sequencing, RNA-Mutect technique and spatial transcriptomics, a handful of hybrid EMT cells with elevated lncCRLA are characterized as the origin of lung adenocarcinoma, which are indiscriminated from hybrid EMT cells by the in-depth sequencing. Plasmatic lncCRLA is properly predictive for the preinvasive lesion of lung adenocarcinoma that would evolve to invasive lesion. That notion is confirmed by a brand-new transgenic mouse model in which EMT is tracked by Cre and Dre system. Dasatinib is potential to hinder the spontaneous progression from preinvasive to invasive lesion of lung adenocarcinoma. Together, plasmatic lncCRLA is defined as a brand-new circulating biomarker to predict the occurrence and evolvement of lung adenocarcinoma, a light for early detection of lung adenocarcinoma.

A novel selenite-tolerant rhizosphere bacterium Wautersiella enshiensis sp. nov., isolated from Chinese selenium hyperaccumulator, Cardamine hupingshanensis.

Selenium (Se) is a dietary essential trace element for humans with various physiological functions and it could also be accumulated by some plant species, like Astragalus bisulcatus, Stanleya pinnata, and Cardamine hupinshanensis. A novel Gram-stain-negative, facultatively anaerobic, selenite-tolerant bacterium, designated strain YLX-1T , was isolated from the rhizosphere of a Se hyperaccumulating plant, Cardamine hupingshanensis in Enshi, China. Phylogenetic analysis based on 16 S rRNA gene sequences indicated that strain YLX-1T is a potential new species in the genus Wautersiella. Strain YLX-1T could grow in the temperature range of 4-37°C (optimally at 28°C) and in the pH range of 5-9 (optimum pH 7), which also could tolerate Se up to 6000 mg Se/L via producing extracellular red nano-Se with 100-300 nm size. However, it could predominantly accumulate selenocystine (SeCys2 ) in the cell under lower Se stress (1.5 mg Se/L). These results would help broaden our knowledge about the Se accumulation and transformation mechanism involved in rhizosphere bacteria like strain YLX-1T in C. hupingshanensis. Based on polyphasic data, we propose the creation of the new species Wautersiella enshiensis sp. nov., strain YLX-1T ( = CCTCC M 2013671) which will be promising to produce nano-Se as fertilizer, food additives or medicine.

Silencing of long noncoding RNA X-inactive specific transcript alleviates Aß1-42-induced microglia-mediated neurotoxicity by shifting microglial M1/M2 polarization.

OBJECTIVES: This experimental study aims to investigate the role of long noncoding RNA X-inactive specific transcript (lncRNA XIST) in the microglial polarization and microglia-mediated neurotoxicity in Alzheimer's disease (AD). METHODS: The levels of XIST and microRNA-107 (miR-107) were detected by quantitative real-time polymerase chain reaction. The spatial learning and memory capability of APPswe/PS1dE9 (APP/PS1) mice were evaluated by the Morris water maze test. The morphology of mouse hippocampus cells was evaluated by hematoxylin and eosin staining. The Iba1-positive microglia were labeled by immunohistochemistry staining. The protein levels were determined by western blot and enzyme-linked immunosorbent assay. Neurotoxicity was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, caspase-3 activity, and Cell Counting Kit-8 assay. The XIST, miR-107, and AD targets were predicted by bioinformatics analysis. RESULTS: The level of XIST was increased in APP/PS1 mice, and XIST silencing ameliorated AD progression. XIST silencing suppressed microglia activation, microglial M1 polarization, and proinflammatory factor levels, but promoted microglial M2 polarization in APP/PS1 mice and Aß1-42-treated BV-2 cells. XIST knockdown reduced Aß1-42-induced microglia-mediated apoptosis and enhanced cell viability in HT22 cells. XIST silencing down-regulated miR-107 level and attenuated Aß1-42-caused suppression of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Those effects of XIST silencing were attenuated by miR-107 inhibitor or LY294002. CONCLUSION: Downregulation of XIST lessened Aß1-42-induced microglia-mediated neurotoxicity by modulating microglial M1/M2 polarization, which may be mediated by the miR-107/PI3K/Akt pathway.

Correction: lncRNA PSMB8-AS1 promotes colorectal cancer progression through sponging miR-1299 to upregulate ADAMTS5.

This corrects the article DOI: 10.4149/neo_2022_220111N42.

Transfer RNAs-derived small RNAs and their application potential in multiple diseases.

The role of tRNAs is best known as adapter components of translational machinery. According to the central dogma of molecular biology, DNA is transcribed to RNA and in turn is translated into proteins, in which tRNA outstands by its role of the cellular courier. Recent studies have led to the revision of the canonical function of transfer RNAs (tRNAs), which indicates that tRNAs also serve as a source for short non-coding RNAs called tRNA-derived small RNAs (tsRNAs). tsRNAs play key roles in cellular processes by modulating complicated regulatory networks beyond translation and are widely involved in multiple diseases. Herein, the biogenesis and classification of tsRNAs were firstly clarified. tsRNAs are generated from pre-tRNAs or mature tRNAs and are classified into tRNA-derived fragments (tRFs) and tRNA halves (tiRNA). The tRFs include five types according to the incision loci: tRF-1, tRF-2, tRF-3, tRF-5 and i-tRF which contain 3' tiRNA and 5' tiRNA. The functions of tsRNAs and their regulation mechanisms involved in disease processes are systematically summarized as well. The mechanisms can elaborate on the specific regulation of tsRNAs. In conclusion, the current research suggests that tsRNAs are promising targets for modulating pathological processes, such as breast cancer, ischemic stroke, respiratory syncytial virus, osteoporosis and so on, and maintain vital clinical implications in diagnosis and therapeutics of various diseases.

lncRNA PSMB8-AS1 promotes colorectal cancer progression through sponging miR-1299 to upregulate ADAMTS5.

Long non-coding RNAs (lncRNAs) have been reported to be vital participants in tumor progression. Recently, lncRNA PSMB8-AS1 has been uncovered to facilitate pancreatic cancer progression by regulating miR-382-3p/STAT1/PD-L1 network. Nonetheless, the role of PSMB8-AS1 and its underlying mechanism have not been well-explored in colorectal cancer (CRC). The expression of RNAs or proteins was detected via qRT-PCR or western blot assays. Functional assays were involved in evaluating the effects of PSMB8-AS1/miR-1299/ADAMTS5 on the malignant behaviors of CRC cells. The molecular mechanism of PSMB8-AS1 was explored via mechanism analyses in CRC cells. Based on experimental results, PSMB8-AS1 expression was notably higher in CRC cell lines than in normal cells. The downregulation of PSMB8-AS1 repressed cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC while promoting cell apoptosis. It was also revealed that PSMB8-AS1 could sponge miR-1299 to upregulate ADAMTS5 in CRC cells. In rescue assays, we further discovered that miR-1299 inhibition or ADAMTS5 overexpression abrogated the suppressive influence of PSMB8-AS1 deficiency on CRC cell growth. In addition, PSMB8-AS1 was validated to induce M2 polarization. In conclusion, PSMB8-AS1 sponges miR-1299 to increase PSMB8-AS1 expression, thus promoting CRC cell growth.

Polysaccharide Krestin Prevents Alzheimer's Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-ß Processing.

Deficits in the clearance of amyloid ß protein (Aß) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aß by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aß clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aß uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aß deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aß clearance by blood monocytes and alleviating AD-like pathology.

c-Src Increases the Sensitivity to TKIs in the EGFR-Mutant Lung Adenocarcinoma.

c-Src and the epidermal growth factor receptor (EGFR) are key apical kinases that govern cell responses to microenvironmental cues. How c-Src affects EGFR-related signaling and targeted therapy remains elusive. Initially, caspase-8 phosphorylated at tyrosine 380 by c-Src predominantly enhancing c-Src activation to facilitate metastasis through attaining epithelial-mesenchymal transition (EMT) phenotype in lung adenocarcinoma. Mechanistically, the linkage of c-Src SH2 domain with phosphotyrosine 380 of caspase-8 and SH3 domain with "PDEP" motif of caspase-8 overactivates c-Src as compared with other c-Src-partner proteins. c-Src is incapable of triggering EGFR-related signaling. This is reflected by the levels of phosphotyrosine 1068, 1086, and 1145, which have no impact on c-Src activation. Tyrosine kinase inhibitors (TKIs) suppress EGFR-related signaling to yield cell deaths of lung adenocarcinoma by both necroptosis and intrinsic apoptosis. Given that c-Src activation is frequent in lung adenocarcinoma, blocking c-Src activation through dasatinib can seal the survival-signaling-related phosphotyrosines of EGFR by its SH2 domain, which in turn increases the antitumor activity of TKIs in EGFR-mutant lung adenocarcinoma. Collectively, c-Src inactivation by dasatinib administration sensitizes EGFR-mutant lung adenocarcinoma to TKIs.

Surface polymer imprinted optical fibre sensor for dose detection of dabrafenib.

Dabrafenib is one of the most widely used of the new generation of targeted anti-cancer drugs. However, its therapeutic window varies for different patients and so there is an unmet need for methods to monitor the dose of drug which the patient receives and at the specific site where it acts. In the case of cancers, it is critical to measure the concentration of drug not just in the bloodstream overall, but in or near tumours, as these will not be the same over multiple time periods. A novel sensor based on an optical fibre long period grating (LPG) modified with a molecular imprinted polymer (MIP) has been developed with the ultimate aim of achieving minimally invasive measurements of Dabrafenib at the tumour site. A molecularly imprinted polymer specific for Dabrafenib was coated on a methacryloylalkoxysilane-functionalised optical fibre long period grating. In vitro experimental results demonstrate that the Dabrafenib sensitivity is 15.2 pm (µg mL-1)-1 (R2 = 0.993) with a limit of detection (LoD) of 74.4 µg mL-1 in serum solution. Moreover, the proposed sensor shows selective response to Dabrafenib over structurally similar 2-Aminoquinoline.

Growth pattern can be used as a new characteristic to predict malignancy in breast cancer.

BACKGROUND: To date, anatomic tumor length is a key criterion for cancer staging and can be used to evaluate the effectiveness of therapies. This article describes growth pattern that can be used as a new characteristic to represent disease burden and tumor features and predict lymphatic metastasis. METHODS: Patients with breast cancer were included in this 10-year (1999-2008) hospital-based multicenter retrospective study. The pathologic length/height ratio was used to illustrate the correlation between tumor features, behaviors and treatments in breast malignancies. The most appropriate ratio was chosen based on the comprehensive evaluation of p value and changing trend of each characteristic. RESULTS: The sample consisted of 4211 women diagnosed with breast cancer. Among them, 2037 patients with complete pathologic length, width and height information were included in the final analysis. There were 2.34 ± 4.77 metastatic lymph nodes for spheroid tumors and 3.21 ± 5.82 for ellipsoid tumors when the cutoff point was 2. In addition, the proportion of ellipsoidal tumors gradually increased from 54.36 to 56.67% in the upper outer quadrant (UOQ) and from 6.7 to 9.03% in the central region with an increase in the cutoff point. The proportion of ER + PR + ellipsoid tumors significantly decreased from 50.1 to 45.35% and that of ER-PR ellipsoid tumors significantly increased from 32.73 to 36.24% with an increase in the cutoff point. Additionally, the best length/weight ratio to distinguish spheroid and ellipsoid tumors was 2. CONCLUSION: This study described for the first time how growth pattern is correlated with tumor malignancy and how it influences the selection of therapeutic strategies for patients.

Resveratrol derivative excited postsynaptic potentiation specifically via PKCß-NMDA receptor mediation.

Several decades have passed since resveratrol (RSV) was first identified in red wine. Researchers have reported the pleiotropic anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, and neuronal protective effects of resveratrol and its glycosylated derivative. However, few studies have distinguished the minute differences in the properties between resveratrol and its glycosylated derivative in terms of synaptic plasticity. As an abundant natural product of glycosylated resveratrol, the derivative 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) has been determined to be a better option for long-term potentiation (LTP) in the hippocampus under physiological and pathological conditions than resveratrol. TSG, as well as its parent molecule RSV, could elicit early-LTP and recover fast excitatory postsynaptic potentials (EPSPs) in the hippocampus. Using various modalities, including pre- and post-whole-cell patch clamping techniques in the calyx of Held, pharmacological inhibition of the N-methyl-d-aspartic acid receptor (NMDAr) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAr) as well as protein kinase C (PKC) activation, we demonstrated that TSG, unlike RSV, could merely promote NMDA-mediated EPSC via PKCß cascade. Our results provide new knowledge that glycosylation of resveratrol could significantly improve its specificity in promoting sole NMDAr mediation of EPSPs, in addition to improving solubility and resistance against oxidation in vivo. These observations could contribute to further exploration of pharmaceutical evaluation of glycosylated stilbene in the future.

SDF-1/CXCR4 axis promotes the growth and sphere formation of hypoxic breast cancer SP cells by c-Jun/ABCG2 pathway.

ATP-binding cassette sub-family G member 2 (ABCG2) confers to the major phenotypes of side population (SP) cells, the cancer stem-like cells. In this study, the SP cells displayed a distinctly higher ABCG2 expression level, sphere formation efficiency (SFE) and growth rate even under hypoxia condition. CXCR4 overexpression by pcDNA-CXCR4 transfection robustly increased ABCG2 expression, and promoted SFE and growth of hypoxic SP cells, while CXCR4 inhibitor AMD3100 could suppress the promotion. Additionally, we found that CXCR4 promoted the expression of c-Jun, a major gene in the oncogenic JNK/c-Jun pathway. Our data on electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays both showed that c-Jun directly bound with the ABCG2 promoter sequence. Moreover, overexpression of JNK/c-Jun promoted ABCG2 expression, SFE, and growth of hypoxic SP cells and the promotion could be rescued by c-Jun inhibitor SP600125. In conclusion, CXCR4 increases the growth and SFE of breast cancer SP cells under hypoxia through c-Jun-mediated transcriptional activation of ABCG2.

RpoN2- and FliA-regulated fliTX is indispensible for flagellar motility and virulence in Xanthomonas oryzae pv. oryzae.

BACKGROUND: Bacterial blight of rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most important crop diseases in the world. More insights into the mechanistic regulation of bacterial pathogenesis will help us identify novel molecular targets for developing effective disease control strategies. A large flagellar gene cluster is regulated under a three-tiered hierarchy by σ54 factor RpoN2 and its activator FleQ, and σ28 factor FliA. A hypothetical protein gene fliTX is located upstream of rpoN2, however, how it is regulated and how it is related to bacterial behaviors remain to be elucidated. RESULTS: Sequence alignment analysis indicated that FliTX in Xoo is less well conserved compared with FliT proteins in Escherichia coli, Salmonella typhimurium, and Pseudomonas fluorescens. Co-transcription of fliTX with a cytosolic chaperone gene fliS and an atypical PilZ-domain gene flgZ in an operon was up-regulated by RpoN2/FleQ and FliA. Significantly shorter filament length and impaired swimming motility were observed in ∆fliTX compared with those in the wildtype strain. ∆fliTX also demonstrated reduced disease lesion length and in planta growth in rice, attenuated ability of induction of hypersensitive response (HR) in nonhost tobacco, and down-regulation of type III secretion system (T3SS)-related genes. In trans expression of fliTX gene in ∆fliTX restored these phenotypes to near wild-type levels. CONCLUSIONS: This study demonstrates that RpoN2- and FliA-regulated fliTX is indispensible for flagellar motility and virulence and provides more insights into mechanistic regulation of T3SS expression in Xoo.

The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147+ breast cancer stem cells.

The cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim to investigate the biological function of SLC34A2 in affecting the stem cell-like phenotypes in BCSCs and its underlying mechanisms. We demonstrated that CD147+ cells from breast cancer tissue samples and cell lines possessed BCSC-like features, including the ability of self-renewal in vitro, differentiation, and tumorigenic potential in vivo. Flow cytometry analysis showed the presence of a variable fraction of CD147+ cells in 9 of 10 tumor samples. Significantly, SLC34A2 expression in CD147+ BCSCs was enhanced compared with that in differentiated adherent progeny of CD147+ BCSCs and adherently cultured cell line cells. In breast cancer patient cohorts, SLC34A2 expression was found increased in 9 of 10 tumor samples. By using lentiviral-based approach, si-SLC34A2-transduced CD147+ BCSCs showed decreased ability of sphere formation, cell viability in vitro, and tumorigenicity in vivo, which suggested the essential role of SLC34A2 in CD147+ BCSCs. Furthermore, PI3K/AKT pathway and SOX2 were found necessary to maintain the stemness of CD147+ BCSCs by using LY294002 or lentiviral-si-SOX2. Finally, we indicated that SLC34A2 could regulate SOX2 to maintain the stem cell-like features in CD147+ BCSCs through PI3K/AKT pathway. Therefore, our report identifies a novel role of SLC34A2 in BCSCs' state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy.

Comparison of analytic performances of Cellsearch and iFISH approach in detecting circulating tumor cells.

Circulating tumor cells (CTCs) have been widely used to predict the prognosis of breast cancer patients. The aim of the present study was to compare the performances of Cellsearch and immunostaining-fluorescence in situ hybridization (iFISH) in detecting CTCs in breast cancer patients. Forty-five newly diagnosed breast cancer patients and 14 healthy donors were recruited and their CTCs were detected by both Cellsearch and iFISH. Correlation between clinicopathological features and CTCs was investigated. We found that the positive rate of CTC detected by iFISH was significantly higher than by Cellsearch system (91% vs 38%). The CTC count, detected either by iFISH or Cellsearch, was not significantly associated with clinical pictures of patients with breast cancer. Therefore, we concluded that, compared to conventional Cellsearch CTC detection, in situ karyotypic identification performed by iFISH had higher detection rate. Therefore, iFISH may be more clinically useful than Cellsearch system.

The Different T-cell Receptor Repertoires in Breast Cancer Tumors, Draining Lymph Nodes, and Adjacent Tissues.

T lymphocytes infiltrate the microenvironment of breast cancer tumors and play a pivotal role in tumor immune surveillance. Relationships between the T-cell receptors (TCR) borne by T cells within tumors, in the surrounding tissues, and in draining lymph nodes are largely unexplored in human breast cancer. Consequently, information about the relative extent of possible T-cell exchange between these tissues is also lacking. Here, we have analyzed the TCR repertoire of T cells using multiplex PCR and high-throughput sequencing of the TCRß chain in the tissues of tumor, adjacent nontumor, and axillary lymph nodes of breast cancer patients. T-cell repertoire diversity in tumors was lower than in lymph nodes, but higher than in nontumor tissue, with a preferential use of variable and joining genes. These data are consistent with the hypothesis that most of the T cells in tumors derive from the lymph node, followed by their expansion in tumor tissue. Positive nodes appeared to enhance T-cell infiltration into tumors and T-cell clonal expansion in lymph nodes. Additionally, the similarity in TCR repertoire between tumor and nontumor tissue was significantly higher in luminal-like, rather than basal-like, breast cancer. Our study elucidated the high heterogeneity of the TCR repertoire and provides potential for future improvements in immune-related diagnosis, therapy, and prognosis for breast cancer patients. Cancer Immunol Res; 5(2); 148-56. ©2016 AACR.

Identification of phenolic compounds that suppress the virulence of Xanthomonas oryzae on rice via the type III secretion system.

The targeting of bacterial type III secretion systems (T3SSs), which are critical virulence factors in most Gram-negative pathogens, is regarded as an alternative strategy for the development of novel anti-microbial drugs. Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc) are two of the most important bacterial pathogens on rice, which cause leaf blight and leaf streak diseases, respectively. To identify potential anti-virulence drugs against these two pathogens, we screened a library of plant phenolic compounds and derivatives for their effects on the Xoo T3SS. Ten of 56 compounds significantly inhibited the promoter activity of a harpin gene, hpa1. These inhibitors were further tested for their impact on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results showed that pretreatment of Xoo with TS006 (o-coumaric acid, OCA), TS010, TS015 and TS018 resulted in significantly attenuated HR without affecting bacterial growth or survival. In addition, Cya translocation assays demonstrated that the translocation of two T3 effectors was suppressed by the four inhibitors. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that mRNA levels of representative genes in the hrp (hypersensitive response and pathogenicity) cluster, as well as the regulatory genes hrpG and hrpX, were reduced by treatment with the four inhibitors, suggesting that expression of the Xoo T3SS was suppressed. The expression of other virulence factors was not suppressed, which indicated possible T3SS-specific inhibition. Finally, we demonstrated that these inhibitors reduced the disease symptoms of Xoo and Xoc on the rice cultivar (Oryza sativa) IR24 to varying extents.

Case report of a Li-Fraumeni syndrome-like phenotype with a de novo mutation in CHEK2.

BACKGROUND: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date. METHODS: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing. RESULTS: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22:29091846, G->A, p.H371Y) was identified in CHEK2, a Li-Fraumeni syndrome causal gene. Examining the status of this novel mutation in the patient's healthy siblings revealed its de novo origin. CONCLUSION: Our study reports the first case of Li-Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease.