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Find video protocols related to scientific articles indexed in Pubmed.
Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome.
BMC Cancer
PUBLISHED: 05-21-2014
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Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer.
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Dissociable effects of psychopathic traits on cortical and subcortical visual pathways during facial emotion processing: an ERP study on the N170.
Psychophysiology
PUBLISHED: 02-10-2014
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This study examined the relation between psychopathic traits and the brain response to facial emotion by analyzing the N170 component of the ERP. Fifty-four healthy participants were assessed for psychopathic traits and exposed to images of emotional and neutral faces with varying spatial frequency content. The N170 was modulated by the emotional expressions, irrespective of psychopathic traits. Fearless dominance was associated with a reduced N170, driven by the low spatial frequency components of the stimuli, and dependent on the tectopulvinar visual pathway. Conversely, coldheartedness was related to overall enhanced N170, suggesting mediation by geniculostriate processing. Results suggest that different dimensions of psychopathy are related to distinct facial emotion processing mechanisms and support the existence of both amygdala deficits and compensatory engagement of cortical structures for emotional processing in psychopathy.
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Identification of previously unrecognized FAP in children with Gardner fibroma.
Eur. J. Hum. Genet.
PUBLISHED: 02-07-2014
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Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner fibroma, may occur sporadically or as a result of inherited predisposition (as part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis often present ?-catenin overexpression (by activating CTNNB1 somatic variants or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma are unknown. We characterized in detail Gardner fibromas diagnosed in two infants to evaluate their role as sentinel lesions of previously unrecognized FAP. In the first infant we found a 5q deletion including APC in the tumor and the novel APC variant c.4687dup in constitutional DNA. In the second infant we found the c.5826_5829del and c.1678A>T APC variants in constitutional and tumor DNA, respectively. None of the constitutional APC variants occurred de novo and both tumors showed nuclear staining for ?-catenin and no CTNNB1 variants. We present the first comprehensive characterization of the pathogenetic mechanisms of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP families.European Journal of Human Genetics advance online publication, 30 July 2014; doi:10.1038/ejhg.2014.144.
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Don't stand so close to me: psychopathy and the regulation of interpersonal distance.
Front Hum Neurosci
PUBLISHED: 01-10-2014
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Psychopathy is characterized by callous and unemotional personality traits, such as reduced empathy and remorse, and a tendency toward deviant interpersonal behaviors. It has been suggested that subtle behavioral cues in individuals with high levels of psychopathic traits may betray their personality during interpersonal interactions, but little research has addressed what these clues might be. In this study, we investigated whether psychopathic traits predict interpersonal distance preferences, which have been previously linked to amygdala functioning. 46 healthy participants performed a behavioral task in which the distance they preferred to maintain between themselves and an experimenter was measured across a series of trials. Psychopathic traits, including Coldheartedness, Fearless Dominance, and Self-centered Impulsivity were assessed using the Psychopathic Personality Inventory-Revised (Lilienfeld and Widows, 2005). Results demonstrated that Coldheartedness predicted preferred interpersonal distance, with more coldhearted participants preferring shorter distances. These findings suggest that interpersonal distance preferences may signal psychopathic traits, particularly callousness, supporting accounts of amygdala dysfunction in psychopathy.
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TGF-? cascade regulation by PPP1 and its interactors -impact on prostate cancer development and therapy.
J. Cell. Mol. Med.
PUBLISHED: 01-08-2014
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Protein phosphorylation is a key mechanism by which normal and cancer cells regulate their main transduction pathways. Protein kinases and phosphatases are precisely orchestrated to achieve the (de)phosphorylation of candidate proteins. Indeed, cellular health is dependent on the fine-tune of phosphorylation systems, which when deregulated lead to cancer. Transforming growth factor beta (TGF-?) pathway involvement in the genesis of prostate cancer has long been established. Many of its members were shown to be hypo- or hyperphosphorylated during the process of malignancy. A major phosphatase that is responsible for the vast majority of the serine/threonine dephosphorylation is the phosphoprotein phosphatase 1 (PPP1). PPP1 has been associated with the dephosphorylation of several proteins involved in the TGF-? cascade. This review will discuss the role of PPP1 in the regulation of several TGF-? signalling members and how the subversion of this pathway is related to prostate cancer development. Furthermore, current challenges on the protein phosphatases field as new targets to cancer therapy will be addressed.
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Prostate cancer: the need for biomarkers and new therapeutic targets.
J Zhejiang Univ Sci B
PUBLISHED: 01-07-2014
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Prostate cancer (PCa) incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men's death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as androgen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa. In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it eventually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards understanding PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.
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Distinct neural activation patterns underlie economic decisions in high and low psychopathy scorers.
Soc Cogn Affect Neurosci
PUBLISHED: 06-06-2013
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Psychopathic traits affect social functioning and the ability to make adaptive decisions in social interactions. This study investigated how psychopathy affects the neural mechanisms that are recruited to make decisions in the ultimatum game. Thirty-five adult participants recruited from the community underwent functional magnetic resonance imaging scanning while they performed the ultimatum game under high and low cognitive load. Across load conditions, high psychopathy scorers rejected unfair offers in the same proportion as low scorers, but perceived them as less unfair. Among low scorers, the perceived fairness of offers predicted acceptance rates, whereas in high scorers no association was found. Imaging results revealed that responses in each group were associated with distinct patterns of brain activation, indicating divergent decision mechanisms. Acceptance of unfair offers was associated with dorsolateral prefrontal cortex activity in low scorers and ventromedial prefrontal cortex activity in high scorers. Overall, our findings point to distinct motivations for rejecting unfair offers in individuals who vary in psychopathic traits, with rejections in high psychopathy scorers being probably induced by frustration. Implications of these results for models of ventromedial prefrontal cortex dysfunction in psychopathy are discussed.
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Carcinoma of the Thyroid With Ewing Family Tumor Elements and Favorable Prognosis: Report of a Second Case.
Int. J. Surg. Pathol.
PUBLISHED: 05-01-2013
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The rare reports of primary, nonneuroendocrine small cell carcinomas of the thyroid have not provided enough evidence to support the recognition of these tumors as an entity or to understand their etiopathogenesis. We report the second case of a primary, nonneuroendocrine small cell carcinoma of the thyroid displaying diffuse expression of cytokeratins, CD99, and p63, in the absence of vimentin expression, in a 24-year-old male who is alive without any signs of disease 13 years after total thyroidectomy and radioactive iodine. The tumor disclosed the EWSR1-FLI1 rearrangement, and we propose to designate it as a carcinoma of the thyroid with Ewing family tumor elements.
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Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain.
Pain
PUBLISHED: 03-28-2013
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The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. Our results show that inflammatory pain caused an impairment of spatial working memory performance that is associated with changes in the activity of the mPFC-MD circuit; an analysis of partial directed coherence between the areas revealed a global decrease in the connectivity of the circuit. This decrease was observed over a wide frequency range in both the frontothalamic and thalamofrontal directions of the circuit, but was more evident from MD to mPFC. In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory.
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Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis.
J. Cell. Mol. Med.
PUBLISHED: 02-11-2013
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Expression of PAX2 (Paired-box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax-2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes-clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma--but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax-2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT-PCR. PAX2 promoter methylation status was assessed by methylation-specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax-2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut-off, Pax-2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax-2 immunoexpression. We concluded that Pax-2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax-2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC.
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POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15).
Mol. Cancer
PUBLISHED: 01-03-2013
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NUP98 gene rearrangements have been reported in acute myeloid leukemia, giving rise to fusion proteins that seem to function as aberrant transcription factors, and are thought to be associated with poor prognosis.
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Exploring the dynamics of P300 amplitude in patients with schizophrenia.
Int J Psychophysiol
PUBLISHED: 05-30-2011
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This study investigated the time-frequency dynamics of P300 generation in patients with first-onset schizophrenia. A group of 40 patients with first-onset schizophrenia and 40 controls performed an auditory oddball task. Wavelet analysis of the single-trial data was used to compute the Event-Related Spectral Perturbation (ERSP) and the Inter-Trial Phase Coherence (ITC) for the delta, theta, alpha, beta and gamma bands on the 50ms window around peak P300 amplitude. The contribution of power and synchrony for P300 amplitudes was studied through correlation and regression analysis. Further, two sub-samples in which patients had lower or higher P300 amplitudes than their control match were contrasted. P300 amplitude did not differ between patients and controls. The frequency domain analysis revealed that controls display larger reductions on gamma power than patients. However, this gamma activity might be the result of micro-saccadic muscular artifacts. Regression analysis shows that P300 amplitude is highly dependent on delta power and synchronization. The analysis of the subsamples confirmed that while gamma power differences are dependent on the diagnosis, delta and theta synchronization are related to P300 amplitude, irrespective of diagnosis.
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Intraepidermal epidermotropic metastatic melanoma: a clinical and histopathological mimicker of melanoma in situ occurring in multiplicity.
J. Cutan. Pathol.
PUBLISHED: 02-24-2011
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The distinction between primary melanoma and melanoma metastatic to the skin has major prognostic implications. We report a case of a 67-year-old male with a diagnosis of a superficial spreading melanoma (stage IB) rendered 6 years earlier who presented clinically with an atypical nevus on his left thigh. Histopathological examination showed an intraepidermal melanocytic proliferation that was interpreted as melanoma in situ. Subsequently, 45 additional pigmented macules appeared in crops over a 9-month period. Clinically and dermoscopically, these lesions were extremely polymorphic. Histopathological findings were compatible with melanoma in situ, as each lesion consisted of a wholly intraepidermal proliferation of markedly atypical melanocytes arranged singly and in nests. A complete gastrointestinal study showed multiple pigmented metastatic lesions throughout the stomach and small bowel, which supported a diagnosis of metastatic melanoma with gastrointestinal and epidermotropic skin involvement. Monosomy of chromosome 9 and a BRAF V600E mutation were detected in the primary tumor sample and in macro-dissected secondary lesions. No CDKN2A or CDK4 germline mutations were found. Intraepidermal epidermotropic metastases of melanoma have been rarely described in literature. In this case, histopathology alone was insufficient to distinguish metastatic melanoma from multiple in situ melanomas. The recognition of epidermotropic metastases should be based on the correlation between clinical, dermoscopic, histopathological and molecular findings.
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Acute megakaryoblastic leukemia with a four-way variant translocation originating the RBM15-MKL1 fusion gene.
Pediatr Blood Cancer
PUBLISHED: 01-13-2011
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Acute megakaryoblastic leukemia (AMKL) with t(1;22)(p13;q13) is a subset of acute myeloid leukemia (AML) representing <1% of all cases and about 70% of pediatric AMKL in the first year of life. We present a case of a 7-month-old female in whom the bone marrow karyotype showed the derivative chromosome der(22)t(1;22)(p13;q13). The RBM15-MKL1 fusion transcript was detected by RT-PCR and confirmed by sequencing analyses. FISH analyses revealed the presence of the four-way translocation t(1;22;17;18)(p13;q13;q22;q12).
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Feasibility of differential diagnosis of kidney tumors by comparative genomic hybridization of fine needle aspiration biopsies.
Genes Chromosomes Cancer
PUBLISHED: 07-15-2010
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The association of a genetic analysis that could improve the diagnostic accuracy of renal cell tumors in biopsy samples would allow better-informed therapeutic decisions. We performed comparative genomic hybridization (CGH) on an ex vivo fine-needle aspiration (FNA) biopsy and a tumor fragment obtained from 75 patients consecutively diagnosed with renal tumors and subjected to radical nephrectomy. The pattern of genomic changes by CGH was used blindly to classify the renal tumors and the genetic findings were subsequently compared with the histopathologic diagnosis. In particular cases, including in two carcinomas with morphologically distinct tumor areas, we performed FISH with several locus-specific probes, and looked for VHL point mutations, exonic rearrangements, or promoter methylation. CGH was successful in 82.7% FNA biopsies and in 96% tumor fragments, with the former allowing genetic diagnosis in 75% of renal cell tumors. The genetic and the initial histological classification differed in two renal neoplasias, but the genetic diagnosis was confirmed after review. The genetic pattern correctly diagnosed 93.5% of clear cell renal cell carcinomas (RCC), 61.5% of chromophobe RCC, 100% of papillary RCC, and 14.3% of oncocytomas, with the negative predictive value being 93.9, 90.7, 100, and 90.2%, respectively. The positive predictive value and specificity of copy number profiles was 100%. We demonstrate that genetic diagnosis by CGH on FNA biopsies can improve differential diagnosis in patients with kidney tumors.
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Endometrial endometrioid adenocarcinoma associated with primitive neuroectodermal tumour of the uterus: a poor prognostic subtype of uterine tumours.
Med. Oncol.
PUBLISHED: 05-12-2010
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Uterine primitive neuroectodermal tumours are extremely rare tumours. They can occur in pure form or combined with another component including endometrioid adenocarcinoma. We aimed to review the clinical impact of neuroectodermal phenotype in uterine tumours, after we recently diagnosed one such case. A 58-year-old female presented with irregular vaginal bleeding. Ultrasonography and CT showed the presence of a large uterine mass with irregular contours. At laparotomy it was found to extend to the right ureter, sigmoid colon and some small intestinal loops. Microscopic examination revealed that the tumour consisted of an endometrioid adenocarcinoma component merging with an extensive neuroectodermal component. No EWSR1 or FUS rearrangement was found in the two tumour components. The patient received two courses of chemotherapy but died 11 months after the initial diagnosis. We reviewed the morphological and molecular criteria for the diagnosis of uterine primitive neuroectodermal tumours published in the literature. We conclude that regardless of the detection of an EWSR1 rearrangement, the presence of a neuroectodermal differentiation component in these rare uterine tumours is a marker of aggressive behaviour, and its presence should be highlighted in the diagnosis.
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Chromosome copy number changes carry prognostic information independent of KIT/PDGFRA point mutations in gastrointestinal stromal tumors.
BMC Med
PUBLISHED: 04-21-2010
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Oncogenic point mutations in KIT or PDGFRA are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive.
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Coexistence of alternative MLL-SEPT9 fusion transcripts in an acute myeloid leukemia with t(11;17)(q23;q25).
Cancer Genet. Cytogenet.
PUBLISHED: 02-02-2010
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We present the characterization at the RNA level of an acute myeloid leukemia with a t(11;17)(q23;q25) and a MLL rearrangement demonstrated by FISH. Molecular analysis led to the identification of two coexistent in-frame MLL-SEPT9 fusion transcripts (variants 1 and 2), presumably resulting from alternative splicing. Real-time quantitative RT-PCR analysis showed that the relative expression of the MLL-SEPT9 fusion variant 2 was 1.88 fold higher than the relative expression of MLL-SEPT9 fusion variant 1. This is the first description of a MLL-SEPT9 fusion resulting in coexistence of two alternative splicing variants, each of which previously found isolated in myeloid leukemias.
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Isolation of phenolic compounds from hop extracts using polyvinylpolypyrrolidone: characterization by high-performance liquid chromatography-diode array detection-electrospray tandem mass spectrometry.
J Chromatogr A
PUBLISHED: 07-31-2009
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The aim of the present work was the development of a suitable methodology for the separation and determination of phenolic compounds in the hop plant. The developed methodology was based on the sample purification by adsorption of phenolic compounds from the matrix to polyvinylpolypyrrolidone (PVPP) and subsequent desorption of the adsorbed polyphenols with acetone/water (70:30, v/v). At last, the extract was analyzed by HPLC-DAD and HPLC-ESI-MS/MS. The first phase of this work consisted of the study of the adsorption behavior of several classes of phenolic compounds (e.g. phenolic acids, flavonols, and flavanols) by PVPP in model solutions. It has been observed that the process of adsorption of the different phenolic compounds to PVPP (at low concentrations) is differentiated, depending on the structure of the compound (number of OH groups, aromatic rings, and stereochemistry hindrance). For example, within the phenolic acids class (benzoic, p-hydroxybenzoic, protocatechuic and gallic acids) the PVPP adsorption increases with the number of OH groups of the phenolic compound. On the other hand, the derivatization of OH groups (methylation and glycosylation) resulted in a greatly diminished binding. The use of PVPP revealed to be very efficient for adsorption of several phenolic compounds such as catechin, epicatechin, xanthohumol and quercetin, since high adsorption and recovery values were obtained. The methodology was further applied for the extraction and isolation of phenolic compounds from hops. With this methodology, it was possible to obtain high adsorption values (>or=80%) and recovery yield values (>or=70%) for the most important phenolic compounds from hops such as xanthohumol, catechin, epicatechin, quercetin and kaempferol glycosides, and in addition it allows the identification of about 30 phenolic compounds by HPLC-DAD and HPLC-ESI-MS/MS.
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Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes.
Leuk. Res.
PUBLISHED: 06-25-2009
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Septins are proteins associated with crucial steps in cell division and cellular integrity. In humans, 14 septin genes have been identified, of which five (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal translocations with the MLL gene in myeloid neoplasias. We have recently shown a significant down-regulation of both SEPT2 and MLL in myeloid neoplasias with the MLL-SEPT2 fusion gene. In this study, we examined the expression pattern of the other 13 known septin genes in altogether 67 cases of myeloid neoplasia, including three patients with the MLL-SEPT2 fusion gene, four with MLL-SEPT6 fusion, and three patients with the MLL-SEPT9 fusion gene. When compared with normal controls, a statistically significant down-regulation was observed for the expression of both MLL (6.4-fold; p=0.008) and SEPT6 (1.7-fold; p=0.002) in MLL-SEPT6 leukemia. Significant down-regulation of MLL was also found in MLL-MLLT3 leukemias. In addition, there was a trend for SEPT9 down-regulation in MLL-SEPT9 leukemias (4.6-fold; p=0.077). Using hierarchical clustering analysis to compare acute myeloid leukemia genetic subgroups based on their similarity of septin expression changes, we found that MLL-SEPT2 and MLL-SEPT6 neoplasias cluster together apart from the remaining subgroups and that PML-RARA leukemia presents under-expression of most septin family genes.
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Both SEPT2 and MLL are down-regulated in MLL-SEPT2 therapy-related myeloid neoplasia.
BMC Cancer
PUBLISHED: 05-15-2009
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A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in MLL-related leukemia. Recently, we have established the MLL-SEPT2 gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified MLL and SEPT2 gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of MLL-SEPT2-associated myeloid neoplasms so far described in the literature.
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CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas.
Mod. Pathol.
PUBLISHED: 04-17-2009
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Renal cell carcinomas comprise a heterogeneous group of tumors. Of these, 80% are clear cell renal cell carcinomas, which are characterized by loss of 3p, often with concomitant gain of 5q22qter. Although VHL is considered the main target gene of the 3p deletions, none has been identified as the relevant target gene for the 5q gain. We have studied 75 consecutive kidney tumors and paired normal kidney samples to evaluate at the genomic and expression levels the tyrosine kinase genes CSF1R and PDGFRB as potential targets in this region. Our findings show that RNA expression of CSF1R, but not of PDGFRB, was significantly higher in clear cell renal cell carcinomas than in normal tissue samples, something that was corroborated at the protein level by immunohistochemistry. The CSF1R staining pattern in clear cell renal cell carcinomas was clearly different from that observed in other renal cell carcinomas, suggesting its potential usefulness in differential diagnosis. FISH analysis demonstrated whole chromosomal gain and relative CSF1R/PDGFRB copy number gain in clear cell renal cell carcinomas, which might contribute to CSF1R overexpression. Finally, one polymorphism and two novel mutations were identified in CSF1R in clear cell renal cell carcinoma patients. Our data allow us to conclude that CSF1R plays a relevant role in clear cell renal cell carcinoma carcinogenesis and raise the possibility that CSF1R may represent a future valuable therapeutic target in these patients.
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Desmoplastic small round cell tumor: diagnosis by fine-needle aspiration cytology.
Acta Cytol.
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Desmoplastic small round cell tumor (DSRCT) is a distinctive clinicopathologic entity with an aggressive clinical course that typically involves the abdominal and/or pelvic peritoneum of young males. A population of small round blue cells and a fibroesclerotic stroma are the usual morphologic features. This tumor is characterized by a typical polyphenotypic profile with expression of epithelial, mesenchymal and neural markers. Cytogenetically, this tumor presents a unique abnormality - t(11;22)(p13;q12).
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Genetic and clinical characterization of 45 acute leukemia patients with MLL gene rearrangements from a single institution.
Mol Oncol
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Chromosomal rearrangements affecting the MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL-related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL-AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL-MLLT3 (27%), a MLL-MLLT1 (20%), or MLL-MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL-MLLT3 fusion (42%), followed by MLL-MLLT10 (23%), MLL-MLLT1 (8%), MLL-ELL (8%), MLL-MLLT4 (4%), and MLL-MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL-MLLT4 fusion variant.
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12q amplification defines a subtype of extraskeletal osteosarcoma with good prognosis that is the soft tissue homologue of parosteal osteosarcoma.
Cancer Genet
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Extraskeletal osteosarcomas are rare tumors with neoplastic cells synthesizing bone, usually associated with poor prognosis. We present the case of a 40-year-old man with an extraskeletal osteosarcoma that was treated by surgery and adjuvant radiotherapy. Thirteen years after the diagnosis, he remains disease-free, without any recurrences or metastases. Histopathological analysis favored the diagnosis of chondroblastic extraskeletal osteosarcoma grade II. G-banding, comparative genomic hybridization (CGH), and real-time PCR for the MDM2 and CDK4 genes were performed to describe the genetic profile of this tumor and revealed aberrations that are common findings of parosteal osteosarcomas. Ring chromosomes, giant marker chromosomes, and a telomeric association were found with G-banding. CGH revealed that 12q was amplified in the ring and giant markers identified by G-banding. Real-time PCR for MDM2 and CDK4 confirmed the amplification of these genes located in 12q. Our findings suggest that a variant of extraskeletal osteosarcoma, which is genotypically similar to parosteal osteosarcoma, exists and is associated with good prognosis.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.