scholarly journals Concurrence of chromosome 6 chromothripsis and glioblastoma metastasis

2017 ◽  
Vol 126 (5) ◽  
pp. 1472-1478 ◽  
Author(s):  
Robert C. Rennert ◽  
Reid R. Hoshide ◽  
Jason W. Signorelli ◽  
Deirdre Amaro ◽  
Jayson A. Sack ◽  
...  
Keyword(s):  
Current Literature ◽  
Copy Number ◽  
Unusual Case ◽  
Tumor Resection ◽  
The Cancer Genome Atlas ◽  
Resected Specimen ◽  
Chromosome 6 ◽  
Data Set ◽  
Cancer Genome Atlas ◽  
Genome Atlas

The authors report an unusual case of a widely metastatic glioblastoma. DNA copy number microarray profile of the resected specimen revealed complex rearrangements found throughout chromosome 6, a phenomenon known as chromothripsis. Such chromothripsis pattern was not observed in 50 nonmetastatic glioblastoma specimens analyzed. Analysis of the 1000+ gliomas profiled by The Cancer Genome Atlas (TCGA) data set revealed one case of chromosome 6 chromothripsis resembling the case described here. This TCGA patient died within 6 months of undergoing tumor resection. Implications of these findings are reviewed in the context of the current literature.

scholarly journals Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship

2010 ◽  
Vol 107 (5) ◽  
pp. 2183-2188 ◽  
Author(s):  
Hyunsoo Kim ◽  
Wei Huang ◽  
Xiuli Jiang ◽  
Brenton Pennicooke ◽  
Peter J. Park ◽  
...  
Keyword(s):  
Copy Number ◽  
The Cancer Genome Atlas ◽  
Glioblastoma Cell ◽  
Methylation Data ◽  
Data Set ◽  
Akt Activation ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Using a multidimensional genomic data set on glioblastoma from The Cancer Genome Atlas, we identified hsa-miR-26a as a cooperating component of a frequently occurring amplicon that also contains CDK4 and CENTG1, two oncogenes that regulate the RB1 and PI3 kinase/AKT pathways, respectively. By integrating DNA copy number, mRNA, microRNA, and DNA methylation data, we identified functionally relevant targets of miR-26a in glioblastoma, including PTEN, RB1, and MAP3K2/MEKK2. We demonstrate that miR-26a alone can transform cells and it promotes glioblastoma cell growth in vitro and in the mouse brain by decreasing PTEN, RB1, and MAP3K2/MEKK2 protein expression, thereby increasing AKT activation, promoting proliferation, and decreasing c-JUN N-terminal kinase-dependent apoptosis. Overexpression of miR-26a in PTEN-competent and PTEN-deficient glioblastoma cells promoted tumor growth in vivo, and it further increased growth in cells overexpressing CDK4 or CENTG1. Importantly, glioblastoma patients harboring this amplification displayed markedly decreased survival. Thus, hsa-miR-26a, CDK4, and CENTG1 comprise a functionally integrated oncomir/oncogene DNA cluster that promotes aggressiveness in human cancers by cooperatively targeting the RB1, PI3K/AKT, and JNK pathways.

scholarly journals A Timely Update of Immunohistochemistry and Molecular Classification in the Diagnosis and Risk Assessment of Endometrial Carcinomas

2021 ◽  
Vol 145 (11) ◽  
pp. 1367-1378
Author(s):  
Minhua Wang ◽  
Pei Hui
Keyword(s):  
Copy Number ◽  
Treatment Strategies ◽  
The United States ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
Cancer Genome Atlas ◽  
Endometrial Carcinomas ◽  
Genome Atlas

Context.— Endometrial carcinoma is the most common gynecologic malignancy in the United States and has been traditionally classified based on histology. However, the distinction of certain histologic subtypes based on morphology is not uncommonly problematic, and as such, immunohistochemical study is often needed. Advances in comprehensive tumor sequencing have provided novel molecular profiles of endometrial carcinomas. Four distinct molecular subtypes with different prognostic values have been proposed by The Cancer Genome Atlas program: polymerase epsilon ultramutated, microsatellite instability hypermutated, copy number low (microsatellite stable or no specific molecular profile), and copy number high (serouslike, p53 mutant). Objective.— To discuss the utilities of commonly used immunohistochemical markers for the classification of endometrial carcinomas and to review the recent advancements of The Cancer Genome Atlas molecular reclassification and their potential impact on treatment strategies. Data Sources.— Literature review and authors' personal practice experience. Conclusions.— The current practice of classifying endometrial cancers is predominantly based on morphology. The use of ancillary testing, including immunohistochemistry, is helpful in the identification, differential diagnosis, and classification of these cancers. New developments such as molecular subtyping have provided insightful prognostic values for endometrial carcinomas. The proposed The Cancer Genome Atlas classification is poised to gain further prominence in guiding the prognostic evaluation for tailored treatment strategies in the near future.

Reannotation and Analysis of Clinical and Chemotherapy Outcomes in the Ovarian Data Set From The Cancer Genome Atlas

2018 ◽  
pp. 1-16 ◽  
Author(s):  
Victor M. Villalobos ◽  
Yan C. Wang ◽  
Branimir I. Sikic
Keyword(s):  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
First Line ◽  
Data Set ◽  
Proteomic Data ◽  
First Line Therapy ◽  
Line Therapy ◽  
Risk Patients ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose The ovarian cancer data set from The Cancer Genome Atlas integrates genomic and proteomic data with clinical annotations based on chart abstractions. We aimed to develop an algorithm to create a matching, more accessible clinical data set cataloging time to treatment failure (TTF) of sequential lines of treatment in patients with serous ovarian cancers. Materials and Methods The master data set of 587 patients with serous ovarian cancer was condensed into a more homogeneous and clinically relevant population comprised of high-risk patients with both grade 3 cancers and stage III or IV disease, resulting in a subgroup of 450 patients. We quantified the TTF of different lines of therapy as well as different therapeutic combinations by extrapolating from the time of starting one therapy to the time of starting a subsequent therapy. Results The overall survival (OS) of patients was highly related to platinum sensitivity status, with median OS times of 56.6, 27.0, and 11.6 months in patients who had platinum-sensitive, -resistant, or -refractory disease, respectively. In high-risk patients, the median TTFs were 14.8, 10.2, 5.7, and 4.1 months with the first, second, third, and fourth lines of chemotherapy, respectively. Patients with stable disease after first-line therapy had similar OS outcomes as patients with partial remissions (34.4 v 33.7 months, respectively). Conclusion This new data set enhances the clinical annotation by providing exploitable chemotherapy benefit data that can now be paired with genomic and proteomic data within The Cancer Genome Atlas data. The major determinant of OS in this study was platinum sensitivity status. TTF decreased with each successive line of therapy. However, patients who achieved only stable disease with first-line therapy had OS similar to those with partial remission.

scholarly journals Enrichment of FGFR3-TACC3 Fusions in Patients With Bladder Cancer Who Are Young, Asian, or Have Never Smoked

2018 ◽  
pp. 1-11
Author(s):  
Amin H. Nassar ◽  
Kevin Lundgren ◽  
Mark Pomerantz ◽  
Eliezer Van Allen ◽  
Lauren Harshman ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Pooled Analysis ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
High Grade ◽  
Data Set ◽  
Dana Farber Cancer Institute ◽  
Cancer Genome Atlas ◽  
Never Smokers ◽  
Genome Atlas

Purpose FGFR3-TACC3 (fibroblast growth factor receptor 3–transforming acidic coiled coil-containing protein 3) fusions have recently been identified as driver mutations that lead to the activation of FGFR3 in bladder cancer and other tumor types and are associated with sensitivity to tyrosine kinase inhibitors. We examined the clinical and molecular characteristics of patients with FGFR3-TACC3 fusions and hypothesized that they are enriched in a subset of patients with bladder cancer. Materials and Methods We correlated somatic FGFR3-TACC3 fusions with clinical and molecular features in two cohorts of patients with bladder cancer. The first cohort consisted of the muscle-invasive bladder cancer (MIBC) data set (n = 412) from The Cancer Genome Atlas. The second cohort consisted of patients with MIBC or high-grade non-MIBC at the Dana-Farber Cancer Institute that had targeted capture sequencing of a selected panel of cancer genes (n = 356). All statistical tests were two sided. The clinical response of one patient with FGFR3-TACC3 bladder cancer to an FGFR3 inhibitor was investigated. Results Overall, 751 patients with high-grade bladder cancer without FGFR3-TACC3 fusions and 17 with FGFR3-TACC3 fusions were identified in the pooled analysis of the data sets from The Cancer Genome Atlas and the Dana-Farber Cancer Institute. FGFR3-TACC3 fusions were enriched in patients age ≤ 50 years versus age 51 to 65 years versus those older than 65 years (pooled, P = .002), and were observed in four (12%) of 33 patients age ≤ 50 years in the pooled analysis. Similarly, FGFR3-TACC3 fusions were significantly more common in Asians (13%) compared with African Americans (4%) and whites (2%; pooled, P < .001), as well as in never smokers (5.6%) compared with ever smokers (1.1%; pooled, P < .001). One patient with the fusion who was treated with an FGFR3 inhibitor achieved complete remission for 10 months. Conclusion Clinical testing to identify FGFR3 fusions should be prioritized for patients with bladder cancer who are younger, never smokers, and/or Asian.

scholarly journals Somatic Copy Number Alterations in Human Cancers: An Analysis of Publicly Available Data From The Cancer Genome Atlas

2021 ◽  
Vol 11 ◽  
Author(s):  
Luuk Harbers ◽  
Federico Agostini ◽  
Marcin Nicos ◽  
Dimitri Poddighe ◽  
Magda Bienko ◽  
...  
Keyword(s):  
Copy Number ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Multiple Cancer ◽  
Human Cancers ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Somatic Copy Number Alterations ◽  
Genome Atlas

Somatic copy number alterations (SCNAs) are a pervasive trait of human cancers that contributes to tumorigenesis by affecting the dosage of multiple genes at the same time. In the past decade, The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) initiatives have generated and made publicly available SCNA genomic profiles from thousands of tumor samples across multiple cancer types. Here, we present a comprehensive analysis of 853,218 SCNAs across 10,729 tumor samples belonging to 32 cancer types using TCGA data. We then discuss current models for how SCNAs likely arise during carcinogenesis and how genomic SCNA profiles can inform clinical practice. Lastly, we highlight open questions in the field of cancer-associated SCNAs.

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