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The main injuries among victims of the terrorist act in the Tokyo subway resulted from sub-lethal inhalation and whole body exposure to sarin vapor. In order to study the long term effects of such exposure and to simulate these conditions, freely moving rats were exposed to sarin vapor (27.2±1.7 µg/l) for 10 min. About 50% of the rats showed no overt symptoms and the rest had mild to moderate clinical symptoms that subsided within 4h following exposure. A reduction of weight was noted during the first 3 days with full recovery on the 4th day. Rat's heart was challenged with epinephrine 1 and 6 months post exposure. A significant reduction in the threshold for epinephrine-induced arrhythmia (EPIA) was noted in rats exposed to sarin. A time dependent increase in the kD and Bmax values of muscarinic auto receptors (M2) was recorded in the rat's cortex and striatum. No changes were recorded in the rats' brain trans locator protein (TSPO) levels, concomitant with no observed changes in the animals' performance in A Morris water maze test. A significant increase in open field activity was noted 6 months following exposure to sarin vapor as well as a significant decrease in prostaglandin E2 (PGE2) production in the brain. It is speculated that down regulation of the M2 auto receptor function, caused hyper reactivity of the cholinergic system which leads to the changes described above. The continuous reduction in M2 auto-receptor system through an unknown mechanism may be the cause for long lasting decline in sarin-exposed casualties' health.

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Epinephrine-induced arrhythmias (EPIA) are known to be associated with local cardiac cholinergic activation. The present study examined the development of QT prolongation and the effect on EPIA of whole-body exposure of animals to a potent acetylcholine esterase inhibitor. Freely moving rats were exposed to sarin vapor (34.2 +/- 0.8 microg/liter) for 10 min. The electrocardiograms (ECG) of exposed and control animals were monitored every 2 weeks for 6 months. One and six months post exposure, rats were challenged with epinephrine under anesthesia, and the threshold for arrhythmias was determined. Approximately 35% of the intoxicated rats died within 24 h of sarin exposure. Additional occasional deaths were recorded for up to 6 months (final mortality rate of 48%). Surviving rats showed, agitation, aggression, and weight loss compared to non-exposed rats, and about 20% of them experienced sporadic convulsions. Sarin-challenged rats with severe symptoms demonstrated QT segment prolongation during the first 2-3 weeks after exposure. The EPIA that appeared at a significantly lower blood pressure in the treated group in the first month after intoxication lasted for up to 6 months. This decrease in EPIA threshold was blocked by atropine and methyl-atropine. Three months post exposure no significant changes were detected in either k(D) or B(max) values of (3)H-N-methyl scopolamine binding to heart homogenates, or in the affinity of carbamylcholine to cardiac muscarinic receptors. The increase in the vulnerability to develop arrhythmias long after accidental or terror-related organophosphate (OP) intoxication, especially under challenging conditions such as stress or intensive physical exercise, may explain the delayed mortality observed following OP exposure.

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BRG1 and Brahma are critical and mutually exclusive subunits of the multi-constituent SWI/SNF chromatin remodeling complexes. These complexes play a key role in transcriptional regulation by dynamically altering chromatin architecture. Although the two proteins are very similar in structure, murine models demonstrate a clear dichotomy in BRG1/BRM function as heterozygous loss of BRG1 results in tumor development whereas homozygous loss of BRM does not. BRG1 and/or BRM protein is absent or disrupted in approximately 17% of all human adenocarcinomas. Concomitant loss is frequent in non-small cell lung carcinomas and incurs a negative prognosis. The mechanism(s) whereby loss of BRG1 (but apparently not BRM) may contribute to tumor development and/or progression is/are ill defined. In this study, we employ MiaPaCa2, a human pancreatic adenocarcinoma cell line that lacks BRM but retains BRG1 expression to evaluate the impact of BRG1 and BRM individually on growth and tumorigenicity. We show that the MiaPaca2 cell line can apparently tolerate only very low levels of BRM after restoration of stable expression. Reduction of expression of BRG1 via shRNAi in stable clones of MiaPaCa2 results in a marked change in morphology and alterations in actin cytoskeletal organization but does not appear to exert a significant effect on in vitro growth of the cell line. Our results implicate a role for the SWI/SNF complex in the regulation of cellular differentiation.

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Loss of heterozygosity and allelic imbalance data has shown that there are two distinct regions of loss on chromosome 18q associated with the progression of prostate cancer (CaP). To investigate the functional significance of chromosome 18q loci in CaP, we utilized the technique of microcell-mediated chromosome transfer to introduce an intact chromosome 18 into the human prostate cancer cell line, PC-3. Three of the resulting hybrid lines were compared to the PC-3 cells in vitro and in vivo. The hybrid cell lines, containing an intact copy of the introduced chromosome 18, exhibited a substantial reduction in anchorage-dependent and independent growth in vitro. These hybrid cell lines also made smaller tumors in nude mice following subcutaneous injection compared to PC-3 cells. Because tumor growth was not completely eliminated by introduction of chromosome 18, we assessed the ability of the hybrids to metastasize to bone after intra-cardiac inoculation in a nude mouse model. Mice inoculated with PC-3 hybrids containing intact copies of chromosome 18 had significantly fewer bone metastases and dramatically improved survival compared to PC-3 cells. In addition, the introduction of chromosome 18 significantly reduced tumor burden in extraskeletal sites. This was not because of differences in growth rates because mice bearing hybrids were monitored for metastases over twice as long as mice bearing PC-3 cells. Taken together, these data suggest that chromosome 18 has a functional role in CaP to suppress growth and metastases. Identification of the responsible gene(s) may lead to molecular targets for drug discovery.

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A cDNA clone encoding human SRBC [serum deprivation response factor (sdr)-related gene product that binds to c-kinase] was isolated in a yeast two-hybrid screening, with amino acids 1-304 of BRCA1 as the probe. The human SRBC gene (hSRBC) was mapped to chromosome region 11p15.5-p15.4, close to marker D11S1323, at which frequent loss of heterozygosity (LOH) has been observed in sporadic breast, lung, ovarian, and other types of adult cancers as well as childhood tumors. hSRBC-coding region mutations including frame shift and truncation mutations were detected in a few ovarian and lung cancer cell lines. More significantly, the expression of hSRBC protein was down-regulated in a large fraction [30 (70%) of 43] of breast, lung, and ovarian cancer cell lines, whereas strong expression of hSRBC protein was detected in normal mammary and lung epithelial cells. The down-regulation of hSRBC expression in cancer cells was associated with hypermethylation of CpG dinucleotides in its promoter region, and 3 (60%) of 5 primary breast tumors and 11 (79%) of 14 primary lung tumors were also found to be hypermethylated. Treatment of breast cancer MCF7 cells with 5'azacytidine and Trichostatin A resulted in expression of hSRBC, confirming DNA methylation as the mode of inactivation. Our results suggest that epigenetic or mutational inactivation of hSRBC may contribute to the pathogenesis of several types of human cancers, marking hSRBC as a candidate tumor suppressor gene.

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OBJECTIVE: Our goal was to determine the influence of chondrocalcinosis on MR imaging in the detection of meniscal tears. MATERIALS AND METHODS: A retrospective review was performed of knee MR imaging and arthroscopy records from two university hospitals between 1996 and 1998. Seventy individuals had radiographic evidence of chondrocalcinosis and underwent knee MR imaging. Thirty-seven of these individuals had undergone arthroscopy for further evaluation of their symptoms. MR imaging sensitivity and specificity in the detection of medial and lateral meniscal tears were calculated in these 37 patients who had radiographic evidence of chondrocalcinosis and in a control group of 34 patients who underwent MR imaging and arthroscopy but did not have knee chondrocalcinosis. RESULTS: In the chondrocalcinosis group, MR imaging sensitivity, specificity, and accuracy for meniscal tear were 78%, 71%, and 78%, respectively, for the lateral meniscus, and 89%, 72%, and 81% for the medial meniscus. The control group showed sensitivity, specificity, and accuracy of 93%, 100%, and 97%, respectively, for the lateral meniscus and 100% in all cases for the medial meniscus. The MR imaging detection of meniscal tears in both the lateral and medial compartments combined is significantly poorer in the presence of chondrocalcinosis (p < 0.005). CONCLUSION: MR imaging sensitivity and specificity for detection of meniscal tear is decreased in the presence of meniscal chondrocalcinosis. Chondrocalcinosis appeared as a high-signal-intensity region on T1-weighted, intermediate-weighted, and inversion recovery sequences. The high signal of chondrocalcinosis on inversion recovery sequence is an interesting observation that to our knowledge has not been previously reported. Radiographic correlation with the MR imaging examination can help prevent overdiagnosing meniscal tears.

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Ewing tumour is characterized by specific chromosome translocations which fuse EWS to a subset of genes encoding ETS transcription factors, most frequently FLI-1. We report the analysis of the expression of various cell cycle regulators both in Ewing tumour derived cell lines and in different cellular models with either inducible or constitutive EWS-FLI-1 cDNA expression. In Ewing cell lines, cyclin D1, CDK4, Rb, p27KIP1 and c-Myc were consistently highly expressed whereas p57KIP2, p15INK4B and p14ARF demonstrated undetectable or low expression levels. The amount of p16INK4A, p21CIP1, p18INKAC and CDK6 was variable from one cell line to the other. The inducible expression of EWS-FLI-1 led to a strong upregulation of c-Myc and a considerable downregulation of p57KIP2. Other proteins did not show evident modification. High c-Myc and very low p57KIP2 expression levels were also observed in neuroblastoma NGP cells constitutively expressing EWS-FLI-1 as compared to parental cells. Analysis of the p57KIP2 promoter indicated that EWS-FLI-1 downregulates, possibly through an indirect mechanism, the transcription of this gene. Finally, we show that ectopic expression of p57KIP2 in Ewing cells blocks proliferation through a complete G1 arrest. These results suggest that the modulation of p57(KIP2) expression by EWS-FLI-1 is a fundamental step in Ewing tumorigenesis.

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OBJECTIVE: To describe a clinical syndrome of cerebellar ataxia associated with muscle coenzyme Q10 (CoQ10) deficiency. BACKGROUND: Muscle CoQ10 deficiency has been reported only in a few patients with a mitochondrial encephalomyopathy characterized by 1) recurrent myoglobinuria; 2) brain involvement (seizures, ataxia, mental retardation), and 3) ragged-red fibers and lipid storage in the muscle biopsy. METHODS: Having found decreased CoQ10 levels in muscle from a patient with unclassified familial cerebellar ataxia, the authors measured CoQ10 in muscle biopsies from other patients in whom cerebellar ataxia could not be attributed to known genetic causes. RESULTS: The authors found muscle CoQ10 deficiency (26 to 35% of normal) in six patients with cerebellar ataxia, pyramidal signs, and seizures. All six patients responded to CoQ10 supplementation; strength increased, ataxia improved, and seizures became less frequent. CONCLUSIONS: Primary CoQ10 deficiency is a potentially important cause of familial ataxia and should be considered in the differential diagnosis of this condition because CoQ10 administration seems to improve the clinical picture.

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Organization of genomic DNA into chromatin aids in the regulation of gene expression by limiting access to transcriptional machinery. The SWI/SNF family of complexes, which are conserved from yeast to humans, are ATP-dependent chromatin-remodeling enzymes required for the transcription of a number of genes in yeast. In humans, the gene encoding the BAF47/hSNF5 subunit of the complex, located at 22q11.2, has been found to be mutated in a number of human tumors including rhabdoid, rhabdomyosarcoma, chronic myeloid leukemia, and CNS tumors such as medulloblastomas and choroid plexus carcinomas. In addition, loss of heterozygosity (LOH) has been reported for the BAF47 region in breast and liver cancer. LOH has also been reported in breast and ovarian cancer within 17q12-25, a gene-rich area including BRCA1, BAF60B, and BAF57. Interestingly, the gene encoding the BAF155/hSWI3 subunit of the complex maps to 3p21-p23, an area of chromosomal deletion seen in a number of human adenocarcinomas including breast, kidney, pancreas, and ovary. To look for abnormalities in these proteins as well as the SWI/SNF complex in general, we have determined the protein status of core human SWI/SNF components BAF170, BAF155, BAF57, BAF53a, and BAF47 in 21 breast cell lines. The complex status in other human tumor cell lines of various tissue types was also examined. We also determined the protein status of the human SWI2 homologues, hBRM/SWI2alpha and BRG1/SWI2beta as well as two other proteins found in human SWI/SNF complexes, BAF180 and BAF250. In this study, we identified the first cell line negative for the BAF57 protein as well as a pancreatic carcinoma cell line negative for both the BRG-1 and hBRM proteins.

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Aberrant regulation of CD44, a transmembrane glycoprotein, has been implicated in the growth and metastasis of numerous tumors. Although both CD44 overexpression and loss have been implicated in tumor progression, the mechanism of CD44 down-regulation in these tumor types is not known. By immunoblot and reverse transcription-polymerase chain reaction analysis we determined that a cervical carcinoma cell line, C33A, lacks CD44 expression. To determine how CD44 is down-regulated in C33A cells, we utilized cell fusions of C33A cells with a CD44-expressing cell line (SAOS-2). We found that SAOS-2 fusion restored CD44 expression in C33A cells, suggesting that a trans-acting factor present in SAOS-2 cells promotes CD44 production. C33A cells are BRG-1-deficient, and we found that CD44 was absent in another BRG-1-deficient tumor cell line, indicating that loss of BRG-1 may be a general mechanism by which cells lose CD44. Reintroduction of BRG-1 into these cells restored CD44 expression. Furthermore, disruption of BRG-1 function through the use of dominant-negative BRG-1 demonstrated the requirement of BRG-1 in CD44 regulation. Finally, we show that Cyclin E overexpression resulted in the attenuation of CD44 stimulation, which is consistent with previous observations that Cyclin E can abrogate BRG-1 action. Taken together, these results suggest that BRG-1 is a critical regulator of CD44 expression, thus implicating SWI/SNF components in the regulation of cellular adhesion and metastasis.

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Nitric oxide (NO) is a key biosignaling molecule produced in both peripheral tissues and the central nervous system by a family of enzymes known as nitric oxide synthases (NOSs). NOSs convert L-arginine to stoichiometric quantities of NO and L-citrulline using molecular oxygen and NADPH as cofactors. Techniques for measurement of NO and NOS activity are essential to demonstrate the role of NO and NO-derived species in biological systems. This unit describes two methods for detection of NO: a direct method employing chemiluminescent detection and one based on quantification of the stable oxidation products with detection using the Griess reagent. Additionally, NOS activity can be quantified by measuring the conversion of radiolabeled L-arginine to radiolabeled L-citrulline.

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OBJECTIVE: The purpose of this study was to determine the extent to which untrained, unlicensed, and unregulated auxiliary dental personnel are permitted by law to expose radiographs. STUDY DESIGN: A survey questionnaire was mailed to the agencies regulating dental practice of the 50 US and 3 regional jurisdictions. Information was requested regarding agency laws regulating who was permitted to prescribe dental radiographs, who was permitted to expose dental radiographs, and who, if anyone, was specifically prohibited. RESULTS: Survey data show that 47.3% of the US population live in jurisdictions that have no regulations prohibiting untrained, unregulated auxiliary dental personnel from exposing patients to ionizing radiation. CONCLUSIONS: The clinical implications for private dental practice in this era of expanding use of auxiliary personnel are that the need exists for increased training and formal licensing of all auxiliary personnel involved in dental radiography.

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Previous work in our laboratory using functional assays for tumorigenicity identified a tumor suppressor element on human chromosome 11q for the cutaneous squamous cell carcinoma cell line A388.6TG.c2. In this report, we screened a variety of agents for differential effects on A388.6TG.c2 compared to a growth-suppressed chromosome 11 microcell hybrid of A388.6TG.c2. One of the agents, 1, 25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3); calcitriol), exerted a growth-altering effect on A388.6TG.c2, which formed rounded cell clusters across the surface of the raft by Day 6 of treatment. In contrast, full-length chromosome 11 hybrids of A388.6TG.c2, as well as two other squamous cell carcinoma cell lines (FaDu and A431), when treated with 1,25(OH)(2)D(3), failed to demonstrate this cell-clumping phenotype. To pursue the hypothesis that the growth suppressor element is involved in altering the response to 1, 25(OH)(2)D(3), we tested microcell hybrids carrying t(X;11) chromosomes lacking large portions of 11q. Although these hybrids, like the parent A388.6TG.c2 cells, demonstrated extensive growth in organotypic cultures, they failed to form cell clusters with 1, 25(OH)(2)D(3) treatment. These results suggest that the chromosome 11 element that alters the response to 1,25(OH)(2)D(3) is distinct from the growth-suppressing element. An examination of differentiation marker expression revealed identical patterns of basal and suprabasal markers for A388.6TG.c2 and for a chromosome 11 hybrid with or without treatment with 1,25(OH)(2)D(3). Finally, characterization of candidate tumor suppressor gene PPP2R1B, which encodes for a subunit of protein phosphatase 2A (PP2A), showed seemingly insignificant alterations by cDNA sequence analysis. Collectively, the data suggest that human chromosome 11 contains two different tumor suppressor elements that may account for the two areas of loss of heterozygosity observed on the long arm of this chromosome.

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PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the factors associated with corneal scarring at baseline. METHODS: We defined corneal scarring as scars that had been detected both by the clinician examining the patient with the slit-lamp biomicroscope and by masked readers of corneal photographs at the CLEK Photography Reading Center. We investigated associations between corneal scarring and patient variables including gender, ethnicity, a family history of keratoconus, a history of ocular trauma, eye rubbing, contact lens wear, rigid contact lens fitting relationships, and corneal findings (such as curvature, Vogt's striae, Fleischer's ring, and central/apical staining). Multiple logistic regression analysis using generalized estimating equations to adjust for the correlation between eyes was used for analysis. RESULTS: The following factors were found to increase the odds of corneal scarring at baseline in the CLEK Study: corneal staining (odds ratios (OR) = 3.40, 95% confidence interval 2.53-4.59), contact lens wear (OR = 3.51, 95% confidence interval 2.27-5.45), Fleischer's ring (OR = 1.63, 95% confidence interval 1.11-2.40), steeper first definite apical clearance lens base curve radius (per diopter, OR = 1.29, 95% confidence interval 1.25-1.33), and age (per decade, OR = 1.54, 95% confidence interval 1.35-1.75). CONCLUSIONS: These baseline data suggest that corneal scarring in keratoconus is associated with corneal staining, contact lens wear, Fleischer's ring, a steeper cornea, and increasing age. The factors that imply added risk for corneal scarring that may be affected by practitioner intervention are staining of the cornea, contact lens wear, and the contact lens fitting relationship.

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Indications for MR imaging have broadened with the development of multiplanar capability, superb soft tissue contrast, and high sensitivity for detecting pathologic alterations. These developments are especially valuable in the analysis of the spine, where multiple anatomic structures reside, each with varying physical properties. MR imaging is unsurpassed in demonstrating early structural and proliferative changes that occur in inflammatory and related arthritides, and in evaluating complications that can cause significant morbidity, and even death. The role of MR imaging in the evaluation of cervical spinal arthritis continues to evolve, as its role in identifying patients for surgical intervention becomes clearer.

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OBJECTIVE: The reported prevention of joint damage during treatment with prednisolone 7.5 mg daily in patients with early rheumatoid arthritis (RA)3 may have important implications for management of RA. We evaluated this observation in another patient population. METHODS: Radiographic progression rates in paired hand radiographs were analyzed in 824 patients with RA who participated in a 3 year prospective, randomized clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (150 or 500 mg bid) and ibuprofen (600 mg qid). Disease modifying antirheumatic drugs (DMARD) were not permitted. Prednisone < or=5 mg daily was continued by 197 patients (mean dose 4.37 mg daily) who had started prednisone therapy at least 6 mo before study entry, but new prednisone starts were not allowed. Standardized hand/wrist radiographs were done yearly and at dropout; joint erosion and narrowing scores of 3 readers were averaged and progression rates were compared. RESULTS: Mean duration of RA was 3.6 years (range 1-7); patients' ages were 21-78 years; 71% were women. Among the 824 patients, those taking prednisone were more likely to have had previous DMARD, and at study entry had higher radiographic scores for joint erosion and joint space narrowing and slightly higher swollen joint counts, C-reactive protein values, and rheumatoid factor titers than those not taking prednisone. However, for the subgroup of 252 patients with RA duration of 12-24 months, prestudy radiographic scores were not different in those taking or not taking prednisone. The mean (+/-SD) monthly rate of increase in erosion scores was 0.228 +/-0.37 for the prednisone patients and 0.206+/-0.35 for patients not taking prednisone (p = 0.994 by ANCOVA). The subgroup with 12 to 24 months' disease duration at entry also showed no significant effect of prednisone treatment on erosion progression. CONCLUSION: Clinically indicated low dose prednisone did not prevent progressive radiographic damage in 197 NSAID treated patients whose physicians had initiated < or =5 mg daily before study entry. The risk/benefit ratio of chronic low dose prednisone in early RA remains uncertain.

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The antiproliferative action of the retinoblastoma tumor suppressor protein, RB, is disrupted in the majority of human cancers. Disruption of RB activity occurs through several disparate mechanisms, including viral oncoprotein binding, deregulated RB phosphorylation, and mutation of the RB gene. Here we report disruption of RB-signaling in tumor cells through loss of a critical cooperating factor. We have previously reported that C33A cells fail to undergo cell cycle inhibition in the presence of constitutively active RB (PSM-RB). To determine how C33A cells evade RB-mediated arrest, cell fusion experiments were performed with RB-sensitive cells. The resulting fusions were arrested by PSM-RB, indicating that C33A cells lack a factor required for RB-mediated cell cycle inhibition. C33A cells are deficient in BRG-1, a SWI/SNF family member known to stimulate RB activity. Consistent with BRG-1 deficiency underlying resistance to RB-mediated arrest, we identified two other BRG-1-deficient cell lines (SW13 and PANC-1) and demonstrate that these tumor lines are also resistant to cell cycle inhibition by PSM-RB and p16ink4a, which activates endogenous RB. In cell lines lacking BRG-1, we noted a profound defect in RB-mediated repression of the cyclin A promoter. This deficiency in RB-mediated transcriptional repression and cell cycle inhibition was rescued through ectopic coexpression of BRG-1. We also demonstrate that 3T3-derived cells, which inducibly express a dominant-negative BRG-1, arrest by PSM-RB and p16ink4a in the absence of dominant-negative BRG-1 expression; however, cell cycle arrest was abrogated on induction of dominant-negative BRG-1. These findings demonstrate that BRG-1 loss renders cells resistant to RB-mediated cell cycle progression, and that disruption of RB signaling through loss of cooperating factors occurs in cancer cells.

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Loss, deletion or rearrangement along large portions of the long arm (q-arm) of chromosome 6 occurs in >80% of late-stage human melanomas, suggesting that genes controlling malignant characteristics are encoded there. Metastasis, but not tumorigenicity, was completely suppressed in the human melanoma cell line C8161 into which an additional intact chromosome 6 had been introduced by microcell-mediated chromosome transfer. Our objective was to refine the location of a putative metastasis suppressor gene. To do this, we transferred an intact (neo6) and a deletion variant [neo6qdel; neo6(del)(q16.3-q23)] of neomycin-tagged human chromosome 6 into metastatic C8161 subclone 9 (C8161.9) by MMCT. Single cell hybrid clones were selected in G-418 and isolated. Following verification that the hybrids retained the expected regions of chromosome 6 using a panel of polymorphic sequence-tagged sites, the hybrids were tested for tumorigenicity and metastasis in athymic mice. As reported previously, intact, normal chromosome 6 suppressed metastasis whether tumor cells were injected i.v. or into an orthotopic (i.e., intradermal) site. In contrast, metastasis was not suppressed in the neo6qdel hybrids. Tumorigenicity was unaffected in hybrids prepared with either chromosome 6 donor. These data strongly suggest that a human melanoma metastasis suppressor locus maps between 6q16.3-q23 ( approximately 40 cM).

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The organization of genomic DNA into chromatin aids in the regulation of gene expression by limiting the access of transcriptional binding domains. The SWI/SNF family of chromatin-remodeling complexes, which are conserved from yeast to humans, open the chromatin to facilitate the transcriptional machinery to access their targets. The gene encoding the BAF47/hSNF5 subunit of the complex has been found mutated in both rhabdoid cell lines and in primary rhabdoid tumors. Since the pediatric tumors rhabdomyosarcoma (RMS) and Wilms' tumor (WT) share a similar genetic link with rhabdoid tumors, it was hypothesized that they may also show alterations of the BAF47 gene. Using primary tumors, the BAF47 protein was detected in all WT but less than 75% of the RMS tested. In cell lines, the BAF47 protein was missing in all rhabdoid cell lines and one RMS cell line. Analysis of sample DNA displayed either a mutation or deletion of the BAF47 gene in all samples negative for the protein. Several other subunits of the human SWI/SNF complex, including BRG1 which is the subunit directly interacting with the Rb tumor suppressor gene, were detected in all tumor samples. Alteration of BAF47 may be a genetic marker associated with the poor prognosis seen in all rhabdoid tumors but only some RMS.

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