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1.
Cancer Lett ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31733288

RESUMO

Cancer is a disease of uncontrolled cell growth and a major cause of death worldwide. Many molecular events characterize tumor initiation and progression. Global gene expression analyses using next-generation sequencing, proteomics and metabolomics show genomic, epigenetic, and metabolite concentration changes in various tumors. Molecular alterations identified include multiple cancer-driving mutations, gene fusions, amplifications, deletions, and post-translational modifications. Data integration from many high-throughput platforms unraveled dysregulation in many metabolic pathways in cancer. Since cancer cells are fast-growing, their metabolic needs are enhanced, hence the requirement for de novo synthesis of essential metabolites. One critical requirement of fast-growing cells and a historically important pathway in cancer is the nucleotide biosynthetic pathway and its enzymes are valuable targets for small molecule inhibition. Purines and pyrimidines are building blocks of DNA synthesis and due to their excessive growth, cancer cells extensively utilize de novo pathways for nucleotide biosynthesis. Methotrexate, one of the early chemotherapeutic agents, targets dihydrofolate reductase of the folate metabolic pathway that is involved in nucleotide biosynthesis. In this review, we discuss the nucleotide biosynthetic pathways in cancer and targeting opportunities.

2.
Hum Pathol ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31698006

RESUMO

Our objective was to evaluate the pathologic features and clinical outcomes in cases of invasive penile squamous cell carcinoma (SCC) and the association with p16 immunohistochemistry (IHC) and human papilloma virus (HPV) in situ hybridization (ISH). A retrospective multi-institutional database search was conducted for invasive SCC of the penis diagnosed between 2007 and 2018 that had undergone surgical resection. Pathologic features, p16 IHC, and HPV ISH were investigated with clinical outcomes. A total of 102 patients were included in the study. The average age was 63±13.3years. Based on histology, 46% of tumors displayed an HPV-related subtype, while p16 was positive in 52% of all cases. Tumor histology correlated well with p16 positivity (P<.001) and p16 IHC accurately predicted the presence of HPV in 25/26 (96%) cases. On multivariate analysis, PNI was associated with local disease recurrence (P=.02) while LVI was associated with progression to metastatic disease (P=.002) and increased overall mortality (P=.02). Urethral involvement was also associated with increased overall mortality (P=.02). In addition, HPV-related tumors based on histologic features correlated with lower rates of metastatic disease (P=.007). HPV is a common cause of penile SCC and can be diagnosed by tumor histology and confirmed by over expression of p16 on IHC. The presence of LVI, PNI, and urethral involvement are poor prognostic indicators while HPV-related tumors based on histology may have lower risk for metastatic disease.

3.
Histopathology ; 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31494951

RESUMO

Among renal cell carcinoma (RCC) the tumor immune microenvironment has been best characterized in clear cell RCC. In this study we investigated the expression of several immune markers including PD-L1, FOXP3, and CD8 in primary and metastatic papillary RCC. Three tissue microarrays were constructed from 78 cases with primary papillary RCC and paired metastatic tumor (24 cases) from 78 patients treated between 1982 and 2014. Immunohistochemistry analysis was performed using commercially available antibodies for PD-L1 (clone E1L3N), FOXP3, CD8 and Ki-67. Markers expression level in tumor and or associated immune cells was analyzed by tissue type (non-tumor vs. primary tumor vs. metastatic tumor) and correlated to clinicopathologic features and outcome. We found PD-L1 expression in up to one quarter of primary and metastatic papillary RCC. On univariate analysis CD8/FOXP3 ratio > 1 was associated with favorable outcome, whereas papillary RCCs with high numbers of dual CD8/Ki-67 positive lymphocytes showed an increased likelihood for tumor progression, overall and cancer-related mortality. The association of CD8/FOXP3 ratio > 1 and high count of CD8/Ki-67 with outcome remained significant on multivariate analysis when adjusting for stage, grade and patient's age. This article is protected by copyright. All rights reserved.

4.
Am J Surg Pathol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31498176

RESUMO

Prostate cancer is well known to metastasize to the testis and is not an uncommon finding on castration performed for advanced disease. Although germ cell tumors make up the majority of testis neoplasms, there are more rare tumors, such as rete testis adenocarcinoma, that can mimic metastatic disease. NKX3.1 and prostein (P501S) are antibodies highly specific for prostate origin. Relatively little is known of the expression of these markers in testicular tissue. We investigated the expression of NKX3.1 and P501S in testicular tissues, sex cord-stromal tumors, germ cell tumors, and rete testis adenocarcinoma. We found strong diffuse nuclear staining for NKX3.1 in Sertoli cells of the testis. Expression of NKX3.1 was seen in 0/3 ovarian Sertoli cell tumors, 1/4 testicular Sertoli cell tumors, and in the Sertoli cell component of 1/12 ovarian Sertoli-Leydig cell tumors. We found moderate, diffuse cytoplasmic positivity for P501S in rete testis epithelium and in testicular Leydig cells. P501S also highlighted Leydig cells in 9/12 Sertoli-Leydig cell tumors of the ovary. Two of 3 Leydig cell tumors of the testis showed weak to moderate, diffuse cytoplasmic staining for P501S. All cases of embryonal carcinoma and pure seminoma were negative for both NKX3.1 and P501S. One case of rete testis adenocarcinoma showed patchy positivity for both NKX3.1 and P501S. In conclusion, NKX3.1 shows routine expression in Sertoli cells and P501S shows routine expression in Leydig cells and rete testis epithelium. In addition, these markers can be positive in sex cord-stromal tumors and rete testis adenocarcinoma.

5.
Virchows Arch ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31482302

RESUMO

Urine cytology is an essential element of the diagnostic work up of hematuria. A significant proportion of cases continue to be placed in the "atypical" or "suspicious" categories of the Paris system for urine cytology, posing difficulty in patient management. We report on the performance of our recently described urine-based assay "UroSEEK" in cases with equivocal diagnosis in patients who are investigated for bladder cancer. Urine samples were collected from two cohorts. The first consisted of patients who presented with hematuria or lower urinary tract symptoms (early detection cohort) and the second of patients that are in follow-up for prior bladder cancer (surveillance cohort). Urine samples were analyzed for mutations in 11 genes and aneuploidy. In the early detection setting, we found high sensitivity and specificity (96% and 88%, respectively) and a strong negative predictive value of 99%. The assay performance was less robust in the surveillance cohort (sensitivity of 74%, specificity of 72%, and negative predictive value of 53%). UroSEEK demonstrated a notable lead time to cancer diagnosis. Seven cases in the early detection cohort and 71 surveillance cases were detected at least 6 months prior to clinical diagnosis. Our results suggest a potential role for UroSEEK assay in guiding management of patients with atypical urine cytology if confirmed in future prospective trials.

6.
Transl Oncol ; 12(11): 1416-1424, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31401334

RESUMO

Cancer cells utilize vitamin folate to fulfill their excessive demand for nucleotides and amino acids. Dihydrofolate reductase (DHFR), an enzyme involved in folate metabolism converts dihydrofolate into tetrahydrofolate, which is required for the de novo synthesis of purines, and certain amino acids. DHFR inhibitors are used as a chemotherapeutic agent. Cancer sequencing analysis has identified additional enzymes in folate metabolism that are dysregulated in cancer. Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), one such enzyme is overexpressed in bladder cancer. MTHFD1L is a mitochondrial enzyme involved in the folate cycle by catalyzing the reaction of formyl-tetrahydrofolate to formate and tetrahydrofolate (THF). THF is crucial for de novo purine and thymidylate synthesis and is also involved in the regeneration of methionine. Cancer cells rely on purines derived from the de novo pathway for the nucleotides whereas normal cells favor the salvage pathway. In this study we examined MTHFD1L expression in bladder cancer. By using publicly available cancer transcriptome data analysis web-portal UALCAN, we found overexpression of MTHFD1L in bladder cancer and expression was associated with overall survival. RT-PCR and immunoblot analysis confirmed the overexpression of MTHFD1L in muscle invasive bladder cancer tissues compared to normal urothelium. Furthermore, our investigations suggested a critical role for MTHFD1L in bladder cancer cell proliferation, colony formation and invasion. Thus, in this study, we show the significance of the folate metabolic enzyme MTHFD1L in aggressive bladder cancers and suggest that being an enzyme, MTHFD1L serves as a valuable therapeutic target.

7.
Prostate ; 79(14): 1629-1639, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31376196

RESUMO

BACKGROUND: Recent microarray and sequencing studies of prostate cancer showed multiple molecular alterations during cancer progression. It is critical to evaluate these molecular changes to identify new biomarkers and targets. We performed analysis of glycine-N-acyltransferase like 1 (GLYATL1) expression in various stages of prostate cancer in this study and evaluated the regulation of GLYATL1 by androgen. METHOD: We performed in silico analysis of cancer gene expression profiling and transcriptome sequencing to evaluate GLYATL1 expression in prostate cancer. Furthermore, we performed immunohistochemistry using specific GLYATL1 antibody using high-density prostate cancer tissue microarray containing primary and metastatic prostate cancer. We also tested the regulation of GLYATL1 expression by androgen and ETS transcription factor ETV1. In addition, we performed RNA-sequencing of GLYATL1 modulated prostate cancer cells to evaluate the gene expression and changes in molecular pathways. RESULTS: Our in silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry, we show that GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low-grade cancers had higher GLYATL1 expression compared to high-grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways. CONCLUSIONS: In summary, our study characterizes the expression of GLYATL1 in prostate cancer and explores the regulation of its regulation in prostate cancer showing role for androgen and ETS transcription factor ETV1. Future studies are needed to decipher the biological significance of these findings.

8.
Virchows Arch ; 475(3): 349-356, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300876

RESUMO

The Cancer Genome Atlas project introduced genomic taxonomy of basal and luminal molecular subtypes in muscle invasive bladder cancer. Fewer studies have addressed the molecular classification in non-muscle invasive bladder cancer (NMIBC). Our aim is to assess the applicability of the proposed phenotypic classification for NMIBC. Three TMAs were constructed from 193 TURBT specimens of 60 bladder cancer patients treated at one of the authors' institutions (1998-2008). Follow-up data on recurrence, grade, or stage progression was obtained. Immunohistochemistry was performed using an automated Ventana System for markers indicative of luminal (GATA3, CK20, ER, Uroplakin II, and HER2/neu) and basal (CK5/6 and CD44) phenotype. Marker expression was evaluated by 3 urologic pathologists. Using unadjusted logistic regression, we found significant association between tumor recurrence at next biopsy and CD44 expression (OR = 2.51, P = 0.03), tumor recurrence at any subsequent biopsy and ER expression (OR = 0.24, P = 0.04), and tumor grade progression at any subsequent biopsy and HER2/neu expression (OR = 0.24, P = 0.04). After adjusting for pathologic stage, we found a significant association between CK5/6 expression and tumor stage progression at either next or any subsequent biopsy (OR = 0.94, P = 0.006; and OR = 0.97, P = 0.02, respectively). Our findings suggest that individual immunohistochemical markers may be of value as prognostic factors in NMIBC.


Assuntos
Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/patologia , Feminino , Fator de Transcrição GATA3/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica/métodos , Queratina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Bexiga Urinária/metabolismo , Urotélio/patologia
9.
Int J Surg Pathol ; : 1066896919865026, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31342804

RESUMO

Prostate cancer can be difficult to appreciate grossly and therefore partial sampling of the gland can lead to incorrect grading, staging, or margin status. However, submitting the entire prostate is more time consuming and costly. We investigated the use of magnetic resonance imaging/ultrasound-targeted biopsy for the selective submission of prostatectomy specimens. We performed a retrospective review for patients with cancer on targeted prostate biopsy who underwent subsequent radical prostatectomy. Prostatectomy specimens were submitted in their entirety and assessed for Grade Group, extraprostatic extension (EPE), margins, and number of blocks. For Targeted-Grossing (TG) assessment, apex margin, bladder neck margin, seminal vesicles, and vas deferens sections were included. For the remainder of the prostate, only sections from areas shown to be positive for cancer on targeted biopsy were included in the analysis. With total tissue submission, EPE was found in 39/81 (48.1%) cases and positive margins in 19/81 (23.5%) cases. The TG method required significantly fewer blocks: 15.8 ± 5.9 versus 44.9 ± 11.9 (P < .0001). The TG method would have diagnosed the correct stage in 73/81 (90.1%) cases, Grade Group in 74/81 (91.4%) cases, and margin status in 79/81 (97.5%) cases. EPE was missed completely by the TG method in 7 cases (P = .008), of which 5/7 (71.4%) had focal EPE. There was no significant difference in stage (P = .24), Grade Group (P = .95), or margin status (P = .16) between the 2 methods. Grossing utilizing selective tissue submission from areas found to be positive for prostate cancer on magnetic resonance imaging/ultrasound-targeted prostate biopsy remains inferior to complete submission of tissue for radical prostatectomy specimens.

10.
Hum Pathol ; 90: 20-26, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075299

RESUMO

Multiparametric magnetic resonance imaging (MRI)/ultrasound fusion targeted prostate biopsy has been shown to outperform systematic biopsy in the detection of clinically significant prostate cancer. Aside from tumor grade, tumor biomarkers such as phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) have prognostic significance in prostate cancer and may help direct management of patients with low-grade tumors. Our objective was to compare the detection of PTEN and ERG expression in MRI-targeted versus systematic prostate biopsies. We compared immunohistochemical expression for PTEN and ERG on prostate biopsy cores from patients with Grade Group (GG) 1 or GG2 prostate cancer who had undergone systematic biopsy with concurrent targeted biopsy. Fifty-three cases had both systematic and MRI-targeted prostate tissue available for staining for PTEN; and 52 cases, for ERG. ERG positivity was seen in 37/52 (71.2%) cases, and PTEN loss was seen in 15/53 (28.3%) cases. The detection of ERG expression was not significantly different between MRI-targeted and systematic biopsy (P = .4). Targeted biopsy was superior to systematic biopsy in the detection of PTEN loss (P = .02). MRI-targeted cores detected 14/15 (93.3%) cases of PTEN loss compared to 7/15 (46.7%) cases detected by systematic cores. Most cases with PTEN loss showed heterogeneous expression in both systematic and targeted cores. In 14/15 (93.3%) cases with PTEN loss, GG was the same between targeted and systematic biopsy. Targeted biopsy is superior to systematic biopsy in the detection of PTEN loss in GG1 and GG2 tumors. Inclusion of targeted cores may be helpful for evaluation of certain prognostic biomarkers.

11.
Mod Pathol ; 32(10): 1544-1550, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31028363

RESUMO

Noninvasive approaches for early detection of bladder cancer are actively being investigated. We recently developed a urine- based molecular assay for the detection and surveillance of bladder neoplasms (UroSEEK). UroSEEK is designed to detect alterations in 11 genes that include most common genetic alterations in bladder cancer. In this study, we analyzed 527 cases, including 373 noninvasive and 154 invasive urothelial carcinomas of bladder from transurethral resections or cystectomies performed at four institutions (1991-2016). Two different mutational analysis assays of a representative tumor area were performed: first, a singleplex PCR assay for evaluation of the TERT promoter region (TERTSeqS) and second, a multiplex PCR assay using primers designed to amplify regions of interest of 10 (FGFR3, PIK3CA, TP53, HRAS, KRAS, ERBB2, CDKN2A, MET, MLL, and VHL) genes (UroSeqS). Overall, 92% of all bladder tumors were positive for at least one genetic alteration in the UroSEEK panel. We found TERT promoter mutations in 77% of low-grade noninvasive papillary carcinomas, with a relatively lower incidence of 65% in high-grade noninvasive papillary carcinomas and carcinomas in situ; p = 0.017. Seventy-two percent of pT1 and 63% of muscle-invasive bladder tumors harbored TERT promoter mutations with g.1295228C>T alteration being the most common in all groups. FGFR3 and PIK3CA mutations were more frequent in low-grade noninvasive papillary carcinomas compared with high-grade noninvasive papillary carcinomas and carcinomas in situ (p < 0.0001), while the opposite was true for TP53 (p < 0.0001). Significantly higher rates of TP53 and CDKN2A mutation rates (p = 0.005 and 0.035, respectively) were encountered in muscle-invasive bladder tumors compared with those of pT1 stage. The overwhelming majority of all investigated tumors showed at least one mutation among UroSEEK assay genes, confirming the comprehensive coverage of the panel and supporting its potential utility as a noninvasive urine-based assay.

12.
Hum Pathol ; 89: 24-32, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026471

RESUMO

Immunotherapy has gained significance in a variety of tumor types including advanced urothelial carcinoma. Noninvasive urothelial lesions have been treated with intravesical Bacillus-Calmette-Guerin (BCG) for decades. Given treatment failure in a subset of these tumors, ongoing clinical trials investigating the role of checkpoint inhibitors are actively pursued in this group of patients. The present study aims to delineate PD-L1, CD8, and FOXP3 expression in tumor microenvironment in non-muscle-invasive urothelial carcinoma samples obtained via sequential biopsies and to assess its potential role in predicting disease outcome. Cases with >1% and> 5% PD-L1 expression in tumor cells showed lower relative risk (RR) to recur at any subsequent biopsy compared with those with lower PD-L1 expression (RRs, 0.83 [P = .009] and 0.81 [P = .03], respectively). Cases with higher expression of FOXP3 in peritumoral lymphocytes were at lower risk for tumor grade progression at any biopsy (RR, 0.2; P = .02). Tumors with FOXP3/CD8 expression ratio of >1 in intratumoral lymphocytes had lower risk of grade progression (RR, 0.28; P = .04). Although higher number of FOXP3-, CD8-, and PD-L1-positive lymphocytes were encountered after BCG treatment, the findings did not reach statistical significance. In patients without BCG treatment, PD-L1 expression in tumor cells and peritumoral lymphocytes varied across serial biopsies, suggesting the need for additional approaches to assess eligibility for immunotherapy in non-muscle-invasive urothelial carcinoma patients.

13.
Virchows Arch ; 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30338346

RESUMO

Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor that plays a crucial role in cell proliferation, growth, differentiation, and apoptosis. IGF1R overexpression has been observed in several cancers, including invasive bladder carcinomas, as a potential prognostic factor. Given known biologic differences between upper and lower urinary tract urothelial carcinoma, we assessed the expression status and prognostic significance of IGF1R in upper tract urothelial carcinoma (UTUC). Two tissue microarrays (TMAs) were built from 99 Japanese patients with non-metastatic UTUC submitted to radical nephroureterectomy between 1997 and 2011. TMAs were constructed with triplicate tumor and paired benign urothelium. Membranous IGF1R staining was evaluated using immunohistochemistry. Two scoring methods were applied (Her2-score and H-score). The highest score was assigned to each tumor. IGF1R positivity was defined as Her2-score ≥ 1+. Association with clinicopathologic parameters and outcome was assessed using hazard ratios (HR) with 95% confidence intervals (CI) and adjusted P values. We found positive IGF1R expression in 70% of UTUC. Outcomes were as follows: tumor recurrence, 33%; tumor progression, 59%; overall mortality, 33%; and cancer-specific mortality, 30%. IGF1R was not associated with any clinicopathologic features. In addition, IGF1R expression was not associated with tumor recurrence (HR = 0.54, CI = 0.25-1.1, P = 0.11), tumor progression (HR = 1.6, CI = 0.8-3.1, P = 0.19), overall mortality (HR = 1.5, CI = 0.68-3.4, P = 0.31), or cancer-specific mortality (HR = 1.6, CI = 0.68-3.8, P = 0.27). Positive IGF1R expression was found in more than two thirds of UTUC. This finding provides a rationale to investigate IGF1R as a potential therapeutic target in UTUC. In contrast to bladder cancer, IGF1R expression in UTUC did not correlate with outcome, further pointing to biologic differences between UTUC and bladder cancer.

14.
Urology ; 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30267727

RESUMO

Most renal masses in the United States are incidentally detected via abdominal imaging. This has led to an increase in the incidence of small renal masses (≤4 cm). Active surveillance is, an oncologically safe option in slow growing and indolent tumors in other organs and has recently become more widely studied in small renal masses. For selected patients, particularly those who harbor significant comorbidities, active surveillance is a safe option for small renal masses. Renal biopsy may be helpful in the decision making process, but remains an optional component for the active surveillance of small renal masses.

16.
Front Mol Neurosci ; 10: 230, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28790889

RESUMO

In the present study, we generated and characterized a splice site-specific monoclonal antibody that selectively detects the calcineurin-binding dynamin1 splice variant dynamin1xb. Calcineurin is a Ca2+-regulated phosphatase that enhances dynamin1 activity and is an important Ca2+-sensing mediator of homeostatic synaptic plasticity in neurons. Using this dynamin1xb-specific antibody, we found dynamin1xb highly enriched in synapses of all analyzed brain regions. In photoreceptor ribbon synapses, dynamin1xb was enriched in close vicinity to the synaptic ribbon in a manner indicative of a peri-active zone immunolabeling. Interestingly, in dark-adapted mice we observed an enhanced and selective enrichment of dynamin1xb in both synaptic layers of the retina in comparison to light-adapted mice. This could be due to an illumination-dependent recruitment of dynamin1xb to retinal synapses and/or due to a darkness-induced increase of dynamin1xb biosynthesis. These latter findings indicate that dynamin1xb is part of a versatile and highly adjustable, activity-regulated endocytic synaptic machinery.

17.
Virchows Arch ; 471(6): 761-767, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28597078

RESUMO

Our group and others have previously demonstrated the presence of TERT promoter mutations (TERT-mut) in 60-80% of urothelial carcinomas and some of their histologic variants. Five other genes have been frequently implicated in bladder cancer: FGRF3, TP53, PIK3CA, HRAS, and CDKN2A. In the current study, we sought to determine the prevalence of mutations in TERT and these five other genes in de novo papillary urothelial neoplasms of low malignant potential (PUNLMP) of the urinary bladder. A retrospective search of our archives for PUNLMP was performed and 30 de novo cases were identified and included in the study. We found mutations in TERT (TERT-mut) and FGFR3 (FGFR3-mut) to be the most common alterations in the cohort (63 and 60%, respectively). The majority of the TERT-mut-positive tumors (84%) had a g.1295228C > T alteration with the remaining tumors demonstrating g.1295250C > T. Approximately one fourth of tumors had TP53 mutations. These findings support the potential utility of a uniform genetic mutation panel to detect bladder cancers of various subtypes.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Virchows Arch ; 471(2): 271-280, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28429075

RESUMO

Empowered by the recent advances in next generation sequencing and bioinformatics technology, an unprecedented wave of integrated transcriptomic and genomic studies have impacted the field of bladder cancer. These studies not only have confirmed previously charted genetic pathways in bladder cancer development but also have led to the discovery of numerous additional crucial driver genetic alterations. As a result, a novel genomic-based taxonomy is emerging that promises to better define clinically relevant intrinsic subtypes of bladder cancer. The current review is an update on the above advances and their significant implications on the future of bladder cancer patient management.


Assuntos
Medicina de Precisão/métodos , Neoplasias da Bexiga Urinária/genética , Biomarcadores Tumorais/genética , Genômica/métodos , Genômica/tendências , Humanos , Medicina de Precisão/tendências
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