RESUMO
The biological heterogeneity of neuroblastoma underscores the need for an in vitro model of each molecularly defined subgroup to investigate tumorigenesis and develop targeted therapies. We have established a permanently growing cell line from a 12-year-old girl who developed a late recurrent stage MS, MDM2-amplified neuroblastoma arising in the liver and performed histological, molecular, cytogenetic, exome, and telomere analyses of the recurrent tumor and the cell line. On histology, the recurrent tumor was immunoreactive for TP53, CDKN1A, and MDM2. A molecular cytogenetic study of the recurrent tumor revealed the amplification of MDM2 but no amplification of MYCN. The established cell line, NBM-SHIM, showed amplification of both MDM2 and MYCN on double-minute chromosomes. A copy number evaluation based on exome data confirmed the finding for MYCN and MDM2 and further identified high ploidy on CDK4 and GLI2 loci in the recurrent tumor and the cell line. The telomere maintenance mechanism on the cell line is unusual in terms of the low expression of TERT despite MYCN amplification and alternative lengthening of telomeres suggested by positive value for C-circle assay and telomere contents quantitative assay. The cell line is unique because it was established from a MYCN-nonamplified, MDM2-amplified, late-relapsed stage MS neuroblastoma, and MYCN amplification was acquired during cell culture. Therefore, the cell line is a valuable tool for investigating neuroblastoma tumorigenesis and new molecular targeted therapies for disrupted ARF-TP53-MDM2 pathway and amplification of MDM2 and CDK4.
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The feasibility of a short-term, three-dimensional (3D) culture-based drug sensitivity test (DST) for surgically resected malignant bone tumors, including osteosarcoma (OS), was evaluated utilizing two OS cell line (KCS8 or KCS9)-derived xenograft (CDX) models. Twenty-three (KCS8) or 39 (KCS9) of 60 tested drugs were likely effective in OS cells derived from a cell line before xenografting. Fewer drugs (19: KCS8, 26: KCS9) were selected as effective drugs in cells derived from a CDX tumor, although the drug sensitivities of 60 drugs significantly correlated between both types of samples. The drug sensitivity of a CDX tumor was not significantly altered after the depletion of non-tumorous components in the sample. In a surgically resected metastatic tumor obtained from a patient with OS, for whom a cancer genome profiling test detected a pathogenic PIK3CA mutation, DST identified mTOR and AKT inhibitors as effective drugs. Of two CDX and six clinical samples of OS and Ewing's sarcoma, DST identified proteasome inhibitors (bortezomib, carfilzomib) and CEP-701 as potentially effective drugs in common. This unique method of in vitro drug testing using 3D-cell cultures is feasible in surgically resected tissues of metastatic malignant bone tumors.
RESUMO
Approximately 20% of patients with transient abnormal myelopoiesis (TAM) die due to hepatic or multiorgan failure. To identify potential new treatments for TAM, we performed in vitro drug sensitivity testing (DST) using the peripheral blood samples of eight patients with TAM. DST screened 41 agents for cytotoxic properties against TAM blasts. Compared with the reference samples of healthy subjects, TAM blasts were more sensitive to glucocorticoids, the mitogen-activated protein kinase kinase (MAP2K) inhibitor trametinib, and cytarabine. Our present results support the therapeutic potential of glucocorticoids and the role of the RAS/MAP2K signalling pathway in TAM pathogenesis.
Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Reação Leucemoide/tratamento farmacológico , Mielopoese/efeitos dos fármacos , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores , Técnicas de Cultura de Células , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Ensaios de Triagem em Larga Escala , Humanos , Imuno-Histoquímica , Reação Leucemoide/etiologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Genetic testing has enabled the diagnosis of multiple congenital anomalies and/or intellectual disabilities. However, because of the phenotypic variability in these disorders, selection of an appropriate genetic test can be difficult and complex. For clinical examination, particularly in clinical facilities, a simple and standardized system is needed. METHODS: We compared microarray comparative genomic hybridization and clinical exome sequencing with regard to diagnostic yield, cost, and time required to reach a definitive diagnosis. After first performing G-banding for 200 patients with multiple congenital anomalies and/or intellectual disability, as a subsequent genetic test, microarray and clinical exome sequencing were compared with regard to diagnostic yield, cost, and time required. RESULTS: There was no obvious difference in the diagnostic rate between the two methods; however, clinical exome sequencing was superior in terms of cost and time. In addition, clinical exome sequencing could sufficiently identify copy number variants, and even smaller copy number variants could be identified. CONCLUSIONS: Clinical exome sequencing should be implemented earlier as a genetic test for undiagnosed patients with multiple congenital anomalies and/or intellectual disabilities. Our results can be used to establish inspection methods in clinical facilities.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Testes Genéticos/métodos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Criança , Pré-Escolar , Hibridização Genômica Comparativa/economia , Hibridização Genômica Comparativa/métodos , Variações do Número de Cópias de DNA , Testes Genéticos/economia , Humanos , Análise em Microsséries/métodos , Sequenciamento do Exoma/economia , Sequenciamento do Exoma/métodosAssuntos
Sequenciamento do Exoma/métodos , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Antineoplásicos/uso terapêutico , Criança , Dasatinibe/uso terapêutico , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , PrognósticoRESUMO
Diamond-Blackfan anemia (DBA) is an inherited anemia with multiple congenital malformations, and mutations in ribosomal protein genes have been identified as the underlying cause. We describe a female patient with mild DBA due to 1p22 deletion, encompassing the gene encoding 60S ribosomal protein L5 (RPL5). Considering previously reported cases together with our patient, we suggest that RPL5 haploinsufficiency might cause a less severe form of DBA than loss-of-function mutations.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Anormalidades Craniofaciais/genética , Hipoplasia do Esmalte Dentário/genética , Deleção de Genes , Doenças do Cabelo/genética , Deficiência Intelectual/genética , Osteogênese Imperfeita/genética , Anormalidades Múltiplas/patologia , Criança , Cromossomos Humanos Par 17/química , Colágeno Tipo I/deficiência , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Anormalidades Craniofaciais/patologia , Hipoplasia do Esmalte Dentário/patologia , Feminino , Doenças do Cabelo/patologia , Proteínas de Homeodomínio/genética , Humanos , Deficiência Intelectual/fisiopatologia , Japão , Osteogênese Imperfeita/patologia , Fatores de Transcrição/deficiência , Fatores de Transcrição/genéticaRESUMO
A 15q11.2 microdeletion (BP1-BP2) is associated with congenital heart diseases (CHDs), developmental delay, and epilepsy. This deletion co-occurs with CHD in 20-30% patients, but a familial case of CHD and a 15q11.2 deletion has not been identified. Here we report the first familial (three siblings) case of total anomalous pulmonary venous return associated with 15q11.2 deletion. Array comparative genomic hybridization identified a ~395 kb deletion at 15q11.2 in patient 1. This deletion was confirmed by fluorescence in situ hybridization in patients 1 and 3 and their asymptomatic father. No deleterious mutation was identified by proband-only exome sequencing of patient 1. One healthy sibling and their mother did not carry the deletion. This deletion is often inherited from asymptomatic parents with an estimated low penetrance of 10.4%. Conversely, we observed high penetrance of this deletion, but secondary copy-number variants or pathogenic variants were not detected in this family.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 15/genética , Síndrome de Cimitarra/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndrome de Cimitarra/patologiaRESUMO
Ehlers-Danlos syndrome classical type is a connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and joint hypermobility. The condition typically results from mutations in COL5A1 or COL5A2 leading to the functional haploinsufficiency. Here, we report of a 24-year-old male with mild intellectual disability, dysmorphic features, and a phenotype consistent with Ehlers-Danlos syndrome classical type. A copy number variant-calling algorithm from panel sequencing data identified the deletions exons 2-11 and duplications of exons 12-67 within COL5A1. Array comparative genomic hybridization confirmed a 94 kb deletion at 9q34.3 involving exons 2-11 of COL5A1, and a 3.4 Mb duplication at 9q34.3 involving exons 12-67 of COL5A1.
Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 9 , Colágeno Tipo V/genética , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Estudos de Associação Genética , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Éxons , Fácies , Genótipo , Humanos , Hibridização in Situ Fluorescente , Masculino , Mutação , Fenótipo , Pele/patologia , Adulto JovemRESUMO
A patient with an unusually mild form of Pelizaeus-Merzbacher disease was studied. Clinically, mild developmental delay with acquisition of assisted walking at 16months and mild spastic tetraplegia were evident, but no nystagmus, cerebellar, or extra-pyramidal signs were present. PLP1 mutation analysis revealed a nucleotide substitution adjacent to the acceptor site of intron 3, NM_000533.4:c.454-9T>G. Expression analysis using the patient's leukocytes demonstrated an additional abnormal transcript including the last 118bp of intron 3. In silico prediction analysis suggested the reduction of wild-type acceptor activity, which presumably evokes the cryptic splicing variant. Putative cryptic transcript results in premature termination, which may explain the mild clinical phenotype observed in this patient.
Assuntos
Mutação , Proteína Proteolipídica de Mielina/genética , Doença de Pelizaeus-Merzbacher/genética , Encéfalo/diagnóstico por imagem , Criança , Análise Mutacional de DNA , Humanos , Íntrons , Leucócitos/metabolismo , Imageamento por Ressonância Magnética , Masculino , Proteína Proteolipídica de Mielina/metabolismo , Doença de Pelizaeus-Merzbacher/diagnóstico por imagem , Doença de Pelizaeus-Merzbacher/metabolismo , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de DoençaRESUMO
Associations between graphemes and colours in a nonsynaesthetic Japanese population were investigated. Participants chose the most suitable colour from 11 basic colour terms for each of 40 graphemes from the four categories of graphemes used in the Japanese language (kana characters, English alphabet letters, and Arabic and kanji numerals). This test was repeated after a three-week interval. In their responses, which were not as temporally consistent as those of grapheme-colour synaesthetes, participants showed biases and regularities that were comparable to those of synaesthetes reported in past studies. Although it has been believed that only synaesthetes, and not nonsynaesthetes, tended to associate graphemes with colours based on grapheme frequency, Berlin and Kay's colour typology, and colour word frequency, participants in this study tended in part to associate graphemes with colours based on the above factors. Moreover, participants that were nonsynaesthetes tended to associate different graphemes that shared sounds and/or meanings (e.g., Arabic and kanji numerals representing the same number) with the same colours, which was analogous to the findings in Japanese synaesthetes. These results support the view that grapheme-colour synaesthesia might have its origins in cross-modal association processes that are shared with the general population.
Assuntos
Associação , Viés , Percepção de Cores/fisiologia , Imaginação , Reconhecimento Visual de Modelos/fisiologia , Adolescente , Feminino , Humanos , Japão , Idioma , Matemática , Transtornos da Percepção/fisiopatologia , Estimulação Luminosa , Tempo de Reação/fisiologia , Estatística como Assunto , Inquéritos e Questionários , Sinestesia , Adulto JovemRESUMO
Next-generation sequencing has enabled the screening for a causative mutation in X-linked intellectual disability (XLID). We identified KIAA2022 mutations in two unrelated male patients by targeted sequencing. We selected 13 Japanese male patients with severe intellectual disability (ID), including four sibling patients and nine sporadic patients. Two of thirteen had a KIAA2022 mutation. Patient 1 was a 3-year-old boy. He had severe ID with autistic behavior and hypotonia. Patient 2 was a 5-year-old boy. He also had severe ID with autistic behavior, hypotonia, central hypothyroidism, and steroid-dependent nephrotic syndrome. Both patients revealed consistent distinctive features, including upswept hair, narrow forehead, downslanting eyebrows, wide palpebral fissures, long nose, hypoplastic alae nasi, open mouth, and large ears. De novo KIAA2022 mutations (p.Q705X in Patient 1, p.R322X in Patient 2) were detected by targeted sequencing and confirmed by Sanger sequencing. KIAA2022 mutations and alterations have been reported in only four families with nonsyndromic ID and epilepsy. KIAA2022 is highly expressed in the fetal and adult brain and plays a crucial role in neuronal development. These additional patients support the evidence that KIAA2022 is a causative gene for XLID.
Assuntos
Transtorno Autístico/genética , Hipotireoidismo Congênito/genética , Deficiência Intelectual/genética , Hipotonia Muscular/genética , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Alelos , Transtorno Autístico/diagnóstico , Transtorno Autístico/patologia , Pré-Escolar , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/patologia , Expressão Gênica , Genes Ligados ao Cromossomo X , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/patologia , Masculino , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/patologia , Linhagem , FenótipoRESUMO
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease characterized by gastrointestinal polyposis and mucocutaneous pigmentation. Germline point mutations in the serine/threonine kinase 11 (STK11) have been identified in about 70% of patients with PJS. Only a few large genomic deletions have been identified. We report on a girl with PJS and multiple congenital anomalies. She had intellectual disability, umbilical hernia, bilateral inguinal hernias, scoliosis, and distinct facial appearance including prominent mandible, smooth philtrum, and malformed ears. She developed lip pigmentation at the age of 12 years but had no gastrointestinal polyps. Array comparative genomic hybridization revealed an approximately 610 kb deletion at 19p13.3, encompassing STK11. Together with previous reports, the identification of common clinical features suggests that microdeletion at 19p13.3 encompassing STK11 constitutes a distinctive phenotype.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 19 , Deficiência Intelectual/genética , Hipotonia Muscular/genética , Síndrome de Peutz-Jeghers/genética , Fenótipo , Criança , Hibridização Genômica Comparativa , Fácies , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/diagnóstico , Hipotonia Muscular/diagnóstico , Síndrome de Peutz-Jeghers/diagnósticoRESUMO
Angelman syndrome (AS) is characterized by severe intellectual disability with ataxia, epilepsy, and behavioral uniqueness. The underlining molecular deficit is the absence of the maternal copy of the imprinted UBE3A gene due to maternal deletions, which is observed in 70-75% of cases, and can be detected using fluorescent in situ hybridization (FISH) of the UBE3A region. Only a few familial AS cases have been reported with a complete deletion of UBE3A. Here, we report on siblings with AS caused by a microdeletion of 15q11.2-q12 encompassing UBE3A at the breakpoint of an inversion at 15q11.2 and 15q26.1. Karyotyping revealed an inversion of 15q, and FISH revealed the deletion of the UBE3A region. Array comparative genomic hybridization (CGH) demonstrated a 467 kb deletion at 15q11.2-q12, encompassing only UBE3A, SNORD115, and PAR1, and a 53 kb deletion at 15q26.1, encompassing a part of SLCO3A1. Their mother had a normal karyotype and array CGH detected no deletion of 15q11.2-q12, so we assumed gonadal mosaicism. This report describes a rare type of familial AS detected using the D15S10 FISH test.
Assuntos
Síndrome de Angelman/genética , Pontos de Quebra do Cromossomo , Inversão Cromossômica , Cromossomos Humanos Par 15 , Deleção de Genes , Ubiquitina-Proteína Ligases/genética , Síndrome de Angelman/diagnóstico , Criança , Pré-Escolar , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Fácies , Humanos , Hibridização in Situ Fluorescente , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , IrmãosRESUMO
In Western countries, gene alterations involving the CRLF2-JAK signaling pathway are identified in approximately 50-60% of patients with Down syndrome-associated acute lymphoblastic leukemia (DS-ALL), and this pathway is considered a potential therapeutic target. The frequency of BTG1 deletions in DS-ALL is controversial. IKZF1 deletions, found in 20-30% of DS-ALL patients, are associated with a poor outcome and EBF1 deletions are very rare (â¼2%). We analyzed 38 patients to determine the frequencies and clinical implications of CRLF2-JAK pathway genetic alterations and recurrent gene deletions in Japanese DS-ALL patients. We confirmed a high incidence of P2RY8-CRLF2 (29%) and JAK2 mutations (16%), though the frequency of P2RY8-CRLF2 was slightly lower than that in Western countries (â¼50%). BTG1 deletions were common in our cohort (25%). IKZF1 deletions were detected in 25% of patients and associated with shorter overall survival (OS). EBF1 deletions were found at an unexpectedly high frequency (16%), and at a significantly higher level in P2RY8-CRLF2-positive patients than in P2RY8-CRLF2-negative patients (44% vs. 4%, P=0.015). Deletions of CDKN2A/B and PAX5 were common in P2RY8-CRLF2-negative patients (48 and 39%, respectively) but not in P2RY8-CRLF2-positive patients (11% each). Associations between these genetic alterations and clinical characteristics were not observed except for inferior OS in patients with IKZF1 deletions. These results suggest that differences exist between the genetic profiles of DS-ALL patients in Japan and in Western countries, and that P2RY8-CRLF2 and EBF1 deletions may cooperate in leukemogenesis in a subset of Japanese DS-ALL patients.
Assuntos
Síndrome de Down/genética , Janus Quinase 2/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Citocinas/genética , Adolescente , Povo Asiático , Criança , Pré-Escolar , Síndrome de Down/complicações , Síndrome de Down/etnologia , Feminino , Deleção de Genes , Dosagem de Genes , Humanos , Japão , Masculino , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Receptores Purinérgicos P2Y/genética , Transdução de Sinais , Adulto JovemRESUMO
Kuechler et al. [2011] reported five patients with interstitial deletions in 8q22.2-q22.3 who had intellectual disability, epilepsy, and dysmorphic features. We report on a new patient with the smallest overlapping de novo deletion in 8q22.3 and refined the phenotype. The proposita was an 8-year-old girl, who developed seizures at 10 months, and her epileptic seizure became severe and difficult to control with antiepileptic drugs. She also exhibited developmental delay and walked alone at 24 months. She was referred to us for evaluation for developmental delay and epilepsy at the age of 8 years. She had intellectual disability (IQ 37 at 7 years) and autistic behavior, and spoke two word sentences at 8 years. She had mild dysmorphic features, including telecanthus and thick vermilion of the lips. Array comparative genomic hybridization detected a 1.36 Mb deletion in 8q22.3 that encompassed RRM2B and NCALD, which encode the small subunit of p53-inducible ribonucleotide reductase and neurocalcin delta in the neuronal calcium sensor family of calcium-binding proteins, respectively. The minimum overlapping region between the present and previously reported patients is considered to be a critical region for the phenotype of the deletion in 8q22.3. We suggest that the deletion in 8q22.3 may represent a clinically recognizable condition, which is characterized by intellectual disability and epilepsy.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 8 , Epilepsia/genética , Estudos de Associação Genética , Deficiência Intelectual/genética , Criança , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Epilepsia/diagnóstico , Fácies , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/diagnóstico , FenótipoRESUMO
17p13.1 Deletion encompassing TP53 has been described as a syndrome characterized by intellectual disability and dysmorphic features. Only one case with a 17p13.1 duplication encompassing TP53 has been reported in a patient with intellectual disability, seizures, obesity, and diabetes mellitus. Here, we present a patient with a 17p13.1 duplication who exhibited obesity and intellectual disability, similar to the previous report. The 9-year-old proposita was referred for the evaluation of intellectual disability and obesity. She also exhibited insulin resistance and liver dysfunction. She had wide palpebral fissures, upturned nostrils, a long mandible, short and slender fingers, and skin hyperpigmentation. Array comparative genomic hybridization (array CGH) detected a 3.2 Mb duplication of 17p13.1-p13.2 encompassing TP53, FXR2, NLGN2, and SLC2A4, which encodes the insulin-responsive glucose transporter 4 (GLUT4) associated with insulin-stimulated glucose uptake in adipocytes and muscle. We suggest that 17p13.1 duplication may represent a clinically recognizable condition characterized partially by a characteristic facial phenotype, developmental delay, and obesity.
Assuntos
Duplicação Cromossômica/genética , Cromossomos Humanos Par 17/genética , Deficiência Intelectual/genética , Obesidade/genética , Moléculas de Adesão Celular Neuronais/genética , Criança , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Fácies , Feminino , Transportador de Glucose Tipo 4/genética , Humanos , Resistência à Insulina/genética , Hepatopatias , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Chromosomal abnormalities involving 19p13.3 have rarely been described in the published literature. Here, we report on a girl with a pure terminal duplication of 6.1 Mb on 19p13.3, caused by an unbalanced translocation der(19)t(10;19)(qter;p13.3)dn. Her phenotype included severe psychomotor developmental delay, skeletal malformations, and a distinctive facial appearance, similar to that of a patient previously reported by Lybaek et al. [Lybaek et al. (2009); Eur J Hum Genet 17:904-910]. These results suggest that a duplication of >3 Mb at the terminus of 19p13.3 might represent a distinct chromosomal syndrome.
Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 19 , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Pré-Escolar , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Fácies , Feminino , Estudos de Associação Genética , Humanos , Hibridização in Situ Fluorescente , FenótipoRESUMO
Transcriptional gene silencing (TGS)--a phenomenon observed in endogenous genes/transgenes in eukaryotes--is a huge hindrance to transgenic technology and occurs mainly when the genes involved share sequence homology in their promoter regions. TGS depends on chromosomal position, suggesting the existence of genomic elements that suppress TGS. However, no systematic approach to identify such DNA elements has yet been reported. Here, we developed a successful novel screening strategy to identify such elements (anti-silencing regions-ASRs), based on their ability to protect a flanked transgene from TGS. A silenced transgenic tobacco plant in which a subsequently introduced transgene undergoes obligatory promoter-homology dependent TGS in trans allowed the ability of DNA elements to prevent TGS to be used as the screening criterion. We also identified ASRs in a genomic library from a different plant species (Lotus japonicus: a perennial legume); the ASRs include portions of Ty1/copia retrotransposon-like and pararetrovirus-like sequences; the retrotransposon-like sequences also showed interspecies anti-TGS activity in a TGS-induction system in Arabidopsis. Anti-TGS elements could provide effective tools to reduce TGS and ensure proper regulation of transgene expression. Furthermore, the screening strategy described here will also facilitate the efficient identification of new classes of anti-TGS elements.