Indeed, the methylation

Indeed, the methylation Tofacitinib Citrate Sigma status of the estrogen receptor and p15INK4B can predict relapse risk in AML patients in clinical remission.26 Futher studies will be required to explore the correlation between SLC6A6 methylation status at diagnosis and prognosis. SLC6A6 is a membrane bound sodium and chloride dependent taurine transporter that has been implicated in retinal and kidney development.27,28 This gene is abundant in proliferating lymphocytes and is a downstream target of p53 and WT1 (Wilms tumor suppressor gene).28,29 Interestingly, an estrogen receptor binding site has been identified in the promoter of the SCL6A6 gene and it has been suggested that taurine uptake is regulated by estrogen via SLC6A6.30 The estrogen receptor is a LEF1 target gene that we showed to be up-regulated in the favourable risk group (Fig.

1E) suggesting that SLC6A6 may function downstream of LEF1.31 Of the genes shown to have significant CpG island methylation, only a small proportion demonstrated a corresponding change in expression levels indicating that additional factors control gene expression levels. While the highest correlation between methylation and expression observed was between decreased methylation and increased expression, a significant proportion of genes were observed to show either increased methylation and increased expression or decreased expression and decreased methylation. This questions the dogma that increased promoter methylation results in gene suppression. A number of studies have recently emerged challenging this dogma suggesting that the mechanisms by which methylation impacts on gene expression have still to be completely characterized.

32�C34 The current studies using integration of global methylation and expression analysis will further increase our understanding of epigenetic regulation of gene expression. In conclusion, we ha
Molecularly targeted therapies are transforming the treatment of cancer at various levels.1 Small molecule inhibitors that target the cancer dependent enzymes raise the possibility of rational approaches to cancer therapy. The wealth of molecular information from the recent genomics technologies offer a remarkable opportunity for new target discovery.2,3 Systems level view of perturbed networks or pathways can provide promising therapeutic strategies.

Glioma is known as a highly cellular tumor with poorly differentiated, round or pleomorphic cells that are occasionally multinucleated, nuclear atypia, anaplasia, endothelial proliferation and pseudopalisading necrosis. Multiple genetic level changes involve in the development of primary Entinostat and secondary gliomas. Hence, inhibitions of multiple targets are essential to control the rapidly growing tumour cells.4 There are two major oncogenic pathways such as PI3K pathway and MAPK pathway.

Results are expressed as seconds (s) or ratio Determination of C

Results are expressed as seconds (s) or ratio. Determination of C-reactive protein level We quantitatively determined CRP levels using an immune turbidimetric assay. Latex particles coated with antibody specific to human CRP aggregated in the presence of CRP from the sample, and formed immune complexes. These immune complexes resulted in an increase in light scattering proportional to the CRP concentration MG132 protocol in the serum sample. Light scattering was measured using turbidity (absorbance) readings. CRP concentration was determined using a calibration curve developed from CRP standards of known concentrations (multistandard), with a linearity of the method range of 0.2�C480 mg/dL.

Determination of D-dimer level D-D levels were determined using a quantitative enzyme-linked immunosorbent assay based on the ��sandwich�� type immunoenzymatic method, with final measurements achieved through fluorescence detection. Assays were performed using a VIDAS Automated Immunoassay System (Biomerieux), with a measurement range of 45�C10.000 ��g/L. The reference value used was <500 ��g/L. Determination of platelet count PLT count was automatically measured using a Pentra 80 cell-counter (Horiba), and confirmed by an indirect manual counting method involving a blood smear that was collected from the patient��s finger. After collection, the blood smear was fixed in methanol for 10 min, and then stained with Giemsa for 20 min before being used. Statistical analysis Continuous data are presented as average value and standard deviation. The student��s t-test for paired samples used to compare values between the 2 stages.

Graphic lines were used for data presentation. The relationship between 2 variables was analyzed using Pearson��s and Kendall��s correlation coefficients. A difference with a p value less than 0.05 (p < 0.05) was considered statistically significant. Data analysis was carried out using the Statistical Package for the Social Sciences 11.5 software (SPSS, Chicago, IL). Results Prothrombin time Data analysis using student��s t-test for paired samples showed a statistically significant difference between PT values before surgery (PT 1) and after surgery (PT 2; t = 3.446, df = 44, p = 0.001; Fig. 1). Fig. 1 PT values before surgery (PT 1) and after surgery (PT 2). The mean PT value declined from 90.38% before surgery to 81.25% after surgery.

Activated partial thromboplastin time Data analysis using student��s t-test for paired samples showed no statistically significant difference between preoperative and postoperative APTT (t = 1,406, df = 44, p = 0.167; Fig. 2). Fig. 2 Pre- and postoperative APTT values. In our study, Entinostat we observed no statistically significant changes in APTT values before and after surgery (33.96 s versus 35.07 s, respectively). This observation could be explained by the fact that patients were receiving heparin medication in prophylactic but not therapeutic doses.

The study was approved by the National Institute on Drug Abuse In

The study was approved by the National Institute on Drug Abuse Institutional Review Board. Parents provided consent for their adolescents to participate, and each adolescent signed an assent form after the study was explained fully and especially all questions answered. Table 1. Demographic information and primary variables of interest across externalizing and nonexternalizing groups Data collection was undertaken as part of a larger study with two main goals: (a) smoking cessation treatment trial (Moolchan et al., 2005) and (b) the relationship between externalizing disorders and treatment resistance (Bagot et al., 2007). The latter study showed that severity of externalizing symptoms predicted continued smoking despite participation in cessation treatment.

The findings from the present study extend to the contribution of psychiatric diagnoses of ODD, ADHD, and CD to the development of tobacco dependence as indexed by changes over time in the number of cigarettes smoked per day over the 2 years following the first puff. Instruments and procedures After a brief phone screen, preeligible participants were invited to the clinic for two assessment visits. During the screening visits, participants underwent a physical examination and provided information about their family history and current or past psychiatric disorders. Psychiatric diagnoses were based on the semistructured, computerized version of the Diagnostic Interview for Children and Adolescents (Reich, 2000), which was administered by a trained interviewer.

The Child Behavior Checklist for parental report (Achenbach, 1991) and Youth Self-Report for adolescent self-report (Achenbach & Dumensi, 2001) were used to quantify severity of externalizing symptomatology. Adolescents with and without an externalizing disorder (ADHD, ODD, or CD) were included in the present analysis. Individuals diagnosed with a mood or an anxiety disorder, psychosis, or abuse Batimastat of substances other than tobacco and marijuana were excluded. Developmental smoking trajectories, cigarettes per day, and FTND scores were obtained through self-report at the time of treatment request. The FTND is a widely used six-item questionnaire that assesses tobacco dependence and has well-established psychometric properties (Hendricks, Prochaska, Humfleet, & Hall, 2008). Adolescents also provided information about their smoking history (e.g., ��How old were you when you smoked your first cigarette?,�� ��How old were you when you took your first puff?,�� and ��At what age did you begin smoking daily?��).

Cessation during the age 20- to 28-year interval was defined usin

Cessation during the age 20- to 28-year interval was defined using the same criteria, except that cessation was for at least twelve months at age 28. While a substantial duration of cessation would be ideal (e.g., at least twelve months) for the age 20 outcome, only a small number of individuals had quit for a year because only 2 years had passed since the age 18 assessment. selleck chemical Demographic characteristics by smoking outcomes are shown in Table 1. Table 1. Demographic Characteristics by Smoking Outcomes Analytic Strategy We used logistic regression models to examine to what extent avoidant coping predicts the absolute probability that an individual would make escalate or quit smoking. The first two models expressed the absolute probability of escalating to daily smoking during the period ages 18�C20 (first model) and 20�C28 (second model) as a function of scoring high on avoidant coping at age 18.

The second set of two models expressed the absolute probability of quitting smoking during the periods 18�C20 (first model) and 20�C28 (second model) as a function of the same variable. All probabilities ranged from 0 to 1 and were generated with Stata’s prvalue function, which uses the delta method to transform the logistic regression model coefficients of interest into probabilities while holding other adjustment covariates at their mean values. See our prior papers for more information about these probability models (e.g., Bricker et al., 2009). In addition to the probability models, we also provide readers the traditionally reported odds ratios from logistic regression models.

With each model, a Wald test for heterogeneity was used to assess the influence of avoidant coping at the quartiles of this measure. A Wald test for interaction was also used to examine the moderating effect of life stress. A linear test for trend was conducted by including an ordered variable (e.g., avoidant coping or stress) in the regression model as a continuous covariate to demonstrate if any monotonic relationship existed between the degree of avoidant coping and the probability of smoking escalation and cessation. Covariates All models adjusted for gender, parents�� highest level of education (less than high school [HS] and greater than or equal to HS), and the condition (i.e., control vs. experimental). In addition, all models accounted for intraclass correlations due to clustering within a school district by using Stata’s cluster variance estimation option. Per HSPP trial design specifications, all 40 districts had one HS per district (Peterson et al., 2000). Therefore, clustering by school district was analytically the same as that by HS. All statistical analyses were conducted Brefeldin_A with Stata Statistical Software (version 10.0).

Finally, REGI�� is a hitherto unrecognized and possibly useful an

Finally, REGI�� is a hitherto unrecognized and possibly useful and sensitive marker for mucosal injury and repair. Acknowledgments Atle vB Granlund is the recipient of a PhD grant from the sellckchem Norwegian University of Science and Technology (NTNU) and Ann Elisabeth ?stvik of a PhD grant from The Liaison Committee between the Central Norway Regional Health Authority (RHA) and NTNU. This work was also supported by a research grant from The Liaison Committee between St. Olav’s University Hospital and the Faculty of Medicine, NTNU. Bj?rn Munkvold, Kari Sl?rdahl and Britt Schulze provided excellent technical assistance. The microarray work was carried out with the support from the National Technology Microarray Platform (Norwegian Microarray Consortium) funded by the Functional Genomics Programme (FUGE) of the Norwegian Research Council.

This work was supported in part by a research grant from The Liaison Committee between St. Olav’s University Hospital and the Faculty of Medicine, NTNU. Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Oesophageal cancer is the sixth most frequent cause of cancer death worldwide (Pisani et al, 1993). Most patients with oesophageal cancer in Japan have squamous cell carcinoma (SCC), while most of those in Western countries have adenocarcinoma. Despite improvements in surgical techniques and perioperative management (Akiyama et al, 1994; Ando et al, 2000), and surgery combined with chemotherapy (Ando et al, 2003) and/or radiotherapy (Ishikura et al, 2003), the prognosis remains poor.

Therefore, for oesophageal SCC patients, novel therapies such as molecular-targeted therapy, including small molecule inhibitors of tyrosine kinases or humanised monoclonal antibodies, are very much needed. The HER family of receptor tyrosine kinases consists of four members: EGFR (HER-1), HER-2, HER-3, and HER-4. The HER family-related signalling is reported to play an important role in modulating cell proliferation, survival, Dacomitinib migration, and differentiation. Despite the large number of ligands so far identified for EGFR and HER-3 and -4, no direct ligand for HER-2 has yet been discovered. As HER-2 is the preferred heterodimerisation partner for all other HER family members, increasing evidence suggests that the primary function of HER-2 is as a co-receptor (Tzahar et al, 1996; Graus-Porta et al, 1997). For example, when ligands such as EGF bind to EGFR, EGFR is heterodimerised with HER-2, leading to the subsequent activation of EGFR tyrosine kinase.

Transformation of Arabidopsis thaliana The pBCH1/dimeric hybrid-I

Transformation of Arabidopsis thaliana The pBCH1/dimeric hybrid-IgG/IgA was introduced into Agrobacterium tumefaciens GV3101 by electroporation selleck catalog using a Gene Pulser II (Bio-Rad, Hercules, CA, USA). Wild-type A. thaliana (ecotype Col-0) plants were grown in a temperature-controlled room with 24 h light at 20��C for 6 wk. A. thaliana plants were transformed via the floral dip method as described previously [34]. For efficient transformation, the floral dip procedure was performed 3 times at intervals of 3 or 4 d. The primary transformants were selected on MS medium supplemented with 20 ��g/ml hygromycin B. After selection, hygromycin B-resistant A. thaliana plants were transferred to soil in pots and then grown under the same conditions as for the wild-type plants.

The recombinant plants were grown within the physical containment level 1-plant (P1P) facility of the University of Shizuoka. DNA analysis Genomic DNA was extracted from the leaves of transgenic A. thaliana plants by boiling in a DNA extraction buffer (100 mM Tris-HCl [pH 9.5], 1 M KCl, 10 mM EDTA). PCR was performed with KOD FX Neo (TOYOBO, Osaka, Japan) using the following specific primer sets: IgG Heavy NotF and IgA-H/NotR for the heavy chain; IgGk NotF and IgGk NotR for the light chain; JCF-Xba and JCR for the J chain; and actin2-F and actin2-R for a house keeping gene ACTIN2 of A. thaliana. mRNA analysis Total RNAs were extracted from the leaves of transgenic plants using an RNeasy Mini Kit (QIAGEN, Hilden, Germany). RT-PCR was performed with an AccessQuick RT-PCR System (Promega) using the same gene-specific primer sets as for DNA analysis.

Protein extraction Leaves of transgenic A. thaliana plants were ground in liquid nitrogen to a fine powder with a mortar and pestle. Soluble proteins were extracted with a protein extraction buffer (10 mM MOPS-KOH [pH 7.5], 150 mM NaCl, 0.5 mM EDTA, protease inhibitor cocktail for plant cell and tissue extracts [Sigma-Aldrich, St. Louis, MO, USA]). Cell debris was removed by centrifugation (21,500 �� g, 10 min, 4��C), and the supernatant was used as a source of plantibodies. The protein concentrations in the extracts were determined with a BCA protein assay kit (Thermo Scientific, Rockford, IL, USA) using BSA (Thermo Scientific) as a standard. SDS-PAGE and immunoblotting Total soluble proteins were separated by SDS-PAGE on a 7.

5% gel (non-reducing conditions; Mini-PROTEAN? TGX? Precast Gels #456-1026, Bio-Rad) and a 12% gel (reducing conditions; Mini-PROTEAN? TGX? Precast Gels #456-1046, Bio-Rad), Dacomitinib and then electrically transferred to a PVDF membrane. Hybrid-IgG/IgA were detected with an SNAP i.d. Protein Detection System (Millipore, Billerica, MA, USA) with HRP-goat anti-mouse IgA (�� chain-specific) (1500 dilution; SouthernBiotech, Birmingham, AL, USA), goat anti-mouse kappa (2 ��g/ml; SouthernBiotech) plus HRP-donkey anti-goat IgG (0.

05, p<0 05, respectively; Fig 5a), and similar to the numbers ob

05, p<0.05, respectively; Fig. 5a), and similar to the numbers observed in LDLR?/?/MPO+/+ mice on chow. Moreover, additional analyses of LDLR?/?/MPO?/?tp animals consistently revealed a strongly reduced expression of pro-inflammatory genes previously implicated in the pathogenesis of NASH (Fig. 5b). For new example, tumor necrosis factor-�� (TNF-��) and IL-1�� mRNA expression were almost two-fold lower in the liver of LDLR?/?/MPO?/?tp mice compared with LDLR?/?/MPO+/+tp mice (p<0.05, p<0.01, respectively). In addition, hepatic IL-6 expression tended to be reduced in LDLR?/?/MPO?/?tp mice relative to LDLR?/?/MPO+/+tp mice, although the difference was not statistically significant. Hepatic monocyte chemoattractant protein-1 (Mcp-1) mRNA expression was over two-fold lower in LDLR?/?/MPO?/?tp mice (p<0.

01), and, consistent with this, their CD68 mRNA expression was also significantly reduced. Taken together, these results show that MPO plays an important role in high-fat diet-induced inflammation of the liver, promoting both inflammatory cell recruitment and cytokine/chemokine expression. Figure 5 General reduction of diet-induced hepatic inflammation in LDLR?/?/MPO?/?tp mice. Reduced High-fat Diet-induced Adipose Tissue Inflammation in LDLR?/?/MPO?/?tp Mice The pathogenesis of NASH is mediated by cross-talk between inflamed adipose tissue and the liver [25]. In order to investigate the potential contribution of adipose tissue-derived factors to the reduced hepatic inflammation in LDLR?/?/MPO?/?tp mice, several inflammatory parameters were investigated.

First of all, Ly-6G staining revealed an absence of neutrophils in visceral adipose tissue in both groups (data not shown). Next, visceral adipose tissue was stained for the macrophage marker F4/80. High-fat diet-induced obesity is characterized by infiltration of macrophages into adipose tissue, where they organize into so-called ��crown-like structures�� surrounding dead adipocytes [21]. Interestingly, adipose tissue of LDLR?/?/MPO?/?tp mice was completely devoid of such crown-like structures, whereas they were readily identifiable in adipose tissue of LDLR?/?/MPO+/+tp mice (Fig. 6a). Quantitative PCR analysis of adipose tissue Mac-1 expression, another macrophage marker, was in line with these results, showing a marked reduction in LDLR?/?/MPO?/?tp animals (p<0.05; Fig. 6b).

Similarly, Cilengitide expression of Mcp-1, a potent chemo-attractant for monocytes, was strongly reduced in the LDLR?/?/MPO?/?tp group (p<0.05; Fig. 6b). Furthermore, adipose tissue expression of the pro-inflammatory adipokines leptin and TNF-�� was lower in LDLR?/?/MPO?/?tp animals, whereas expression of adiponectin, which has anti-inflammatory properties, was higher (Fig. 6c). Thus, MPO deficiency protects adipose tissue from high-fat diet-induced inflammation, which may contribute to the attenuation of inflammation in the liver of LDLR?/?/MPO?/?tp mice.

Creatinine went up to

Creatinine went up to they 215 ��mol/L, 12 wk after starting therapy. The patient showed a virological response and since the nephropathy was not related to interferon it was decided to continue a full course of treatment. The third patient had only a mild elevation of serum creatinine from 168 ��mol/L before treatment to 199 ��mol/L at the end of treatment; however, he also underwent a kidney biopsy before starting treatment and has shown MPGN, which has no contraindication to treatment, and indeed if HCV related, may respond well to antiviral therapy. These three patients who developed abnormal renal function and underwent kidney biopsies had an excellent ETR and 2 of them had SVR at 24 wk post therapy.

There was no significant change in GFR during or after therapy from baseline except in the only patient who had rejection who had a decrease in GFR from 61 mL/min to 38 mL/min at the end of therapy. Serum creatinine and GFR remained stable during the treatment period (Table (Table11). Impact of type of immunosuppression There was no relation observed between response rate and the type of immunosuppression regimen used during therapy. There was no relation between the increase of creatinine or decrease in GFR rate and the type of immunosuppression regimen used. Impact of gender, duration post transplant and age on the parameters at the end of therapy period Stratification by gender, duration post transplant and age had no impact on the final post transplant levels of the parameters measured (Tables (Tables3,3, ,4,4, and and55).

Table 3 Impact of patient gender on the parameters at the end of therapy Table 4 Impact of duration post transplant on the parameters at the end of therapy Table 5 Impact of age on the parameters at the end of therapy Table Table66 summarises recent reports on the efficacy and rejection rate following the use of interferon in post renal transplant HCV infection. It shows that there is a high rate of response to PEG-IFN especially when it is combined with ribavirin, compared to conventional interferon. Furthermore, the rate of rejection and graft failure with this type of therapy is much lower than that with conventional interferon (Table (Table66). Table 6 Summary of some reports on the efficacy and rejection rate following the use of interferon alone or in combination with ribavirin in post renal transplant hepatitis C virus infection DISCUSSION Several studies have shown a negative impact of HCV on patient and graft survival post renal transplantation[12-15,19,25,26].

Immunosuppressive therapy after renal transplantation usually leads to a flare up of HCV viremia[28]. In the setting of renal and other organ transplantation, HCV infected post transplant patients have an aggressive and rapidly GSK-3 progressive liver disease with cirrhosis, liver failure and death[12,22,23,36,37].

The analysis of each variable was performed on the change from ba

The analysis of each variable was performed on the change from baseline values, using two tailed student ��t�� test. A ��P�� value less than or equal to 0.05 was considered statistically significant. In addition, the demographic variables were analyzed using Pearson’s chi-square test. At each visit, patients were enquired about any complaints selleck chemicals Lapatinib that might have indicated an adverse drug reaction such as hyperemia, burning/ stinging, blurred vision, corneal ulceration and keratitis. Any such adverse reaction reported was recorded and analyzed. RESULTS Sixty patients (42 males and 18 females) with mean age of 10.26 �� 3.86 years (range 4-18 years) with clinically diagnosed acute SAC were enrolled in the study and evaluated for efficacy and safety of both the drugs.

Differences in demographic characteristics and medical histories were statistically non-significant between the two groups (P > 0.05) [Table 2]. No serious adverse events were reported during the study. Minor adverse reaction included initial burning and stinging on instillation of medication (Group A 6.67%, Group B 10%). However, this did not indicate the discontinuation of the therapy. With diclofenac treatment, the mean scores for all the signs and symptoms were significantly one grade lower at midweek and at the end of the study than baseline values (except for conjunctival mucous and keratitis). Mean values for itching decreased from 3.0 at baseline to 1.16 at the end of study. Evaluation of other ocular symptoms (e.g.

, burning / stinging, discharge / tearing, photophobia, foreign body sensation and swollen eye) at mid-week and at the study end showed lower mean values in diclofenac group than the ketorolac treated eyes [Table 3 and Figure 1]. For conjunctival inflammation, there was a significant treatment response favoring diclofenac over ketorolac at mid-week (P < 0.001) and study end (P < 0.001). The signs of lid oedema and conjunctival chemosis did not show much improvement after day, 3 and the values remained the same till the study end for both the groups. However, conjunctival mucous and keratitis did not show any improvement at all with any of the therapies [Table 4, Figure 2]. An evaluation of the therapeutic response at the completion of the treatment revealed that the number of patients reporting no change in signs and symptoms were more in ketorolac treated groups [Table 5].

Table 2 Pre trial, pretreatment patient characteristics: Group comparisons �C Demographics in the study Table 3 Summary of overall evaluation: Mean scores (symptoms) as seen in the study Figure 1 Symptom evaluation at day 7 in the study Table 4 Summary of overall evaluation: Mean Brefeldin_A scores (signs) seen in the study Figure 2 Sign evaluation at day 7 in the study Table 5 Evaluation of the therapeutic response at the end of study DISCUSSION Acute SAC is a condition accounting for 50% of the ocular allergies.

To maintain sorting efficiencies at relatively high levels (>80%)

To maintain sorting efficiencies at relatively high levels (>80%) and high yields and purities of sorted samples the differential pressure of the core and the sheath fluids can be increased but cannot be >1. Slow sort rates while maintaining optimal differential pressure of flow stream improves efficiency of sorts and the overall yield of intact nuclei. However the greatest variable in our sorting was the origin of the tissue. For example TNBC sorted more efficiently than did PDA samples for both FF and FFPE samples. Gating based on DNA content provides a robust quantitative measure for identifying and sorting tumor populations from samples of interest. For example the 3.0N population sorted from a FF PDA sample was detected 3 years later in an FFPE sample from the same tissue (Figure 5).

The ploidy and the relative distribution of each population present in a biopsy can be recovered by fitting the G0/G1 and G2/M peaks as Gaussian curves and the S phase distribution as a Gaussian broadening distribution. The DNA content histograms from tumor tissue are frequently suboptimal (broad c.v��s, high debris and aggregation) and often complex (multiple overlapping peaks and cell cycles) with frequent skewing and non-Gaussian peak shapes. This is even truer for FFPE specimens that often contain higher levels of damaged or fragmented nuclei (debris) resulting in events usually most visible to the left of the diploid G1 peak and that fall rapidly to baseline (Figures S4,S9). For reproducible phase measurements we typically acquire 10,000 events.

However if a substantial proportion of events are from debris or aggregates, the total number of events acquired must be correspondingly higher in order to assure the required minimum number of intact single nuclei for accurate curve fitting. Different reports have shown that tumor cells can be efficiently sorted from FFPE samples with DNA content based assays and used for genomic analysis [35], [36]. These studies have typically relied on PCR based assays including SNP arrays. These assays have limited resolution based on the ability to distinguish homozygous from partial copy number losses, the mapping of breakpoints and focal amplicons, and in the number of genes and loci interrogated. Furthermore SNP arrays typically require the preparation of platform-specific reduced complexity samples for optimal results limiting the utility of DNA prepared from each sorted sample.

In contrast our methods use whole genome templates that are compatible with a wide variety of high definition assays including aCGH and NGS. For aCGH analysis, short DNAse 1 digestion of genomic DNAs extracted directly from sorted nuclei or with amplified DNAs from FF or FFPE samples provides uniform templates for labeling [32]. The resolution of our assays with purified sorted samples enables discrimination of single copy loss from homozygous loss and the AV-951 mapping of amplicon and deletion boundaries in each tumor genome.