Evaluation of the Prognostic Performance of a 12-gene Glioblastoma Signature Among Low-Grade Glioma Patients in the Cancer Genome Atlas Database

Author(s):  
B. Huff ◽  
I.R. Crocker ◽  
W.J. Curran ◽  
H.K.G. Shu
2014 ◽  
Vol 36 (4) ◽  
pp. E23 ◽  
Author(s):  
David D. Gonda ◽  
Vincent J. Cheung ◽  
Karra A. Muller ◽  
Amit Goyal ◽  
Bob S. Carter ◽  
...  

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.


2017 ◽  
Vol 16 ◽  
pp. 117693511773484
Author(s):  
Nan Hu ◽  
Haojie Cheng ◽  
Kevin Zhang ◽  
Randy Jensen

Background: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Previous studies on GBM biomarkers focused on the effect of the biomarkers on overall survival (OS). Until now, no study has been published that evaluates the performance of biomarkers for prognosing OS. We examined the performance of microRNAs, gene expressions, gene signatures, and methylation that were previously identified to be prognostic. In addition, we investigated whether using clinical risk factors in combination with biomarkers can improve the prognostic performance. Methods: The Cancer Genome Atlas, which provides both biomarkers and OS information, was used in this study. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the prognostic accuracy. Results: For prognosis of OS by 2 years from diagnosis, the area under the ROC curve (AUC) of microRNAs, Mir21 and Mir222, was 0.550 and 0.625, respectively. When age was included in the risk prediction score of these biomarkers, the AUC increased to 0.719 and 0.701, respectively. The SAMSN1 gene expression attains an AUC of 0.563, and the “8-gene” signature identified by Bao achieves an AUC of 0.613. Conclusions: Although some biomarkers are significantly associated with OS, the ability of these biomarkers for prognosing OS events is limited. Incorporating clinical risk factors, such as age, can greatly improve the prognostic performance.


2017 ◽  
pp. 1-12
Author(s):  
Manish R. Sharma ◽  
James T. Auman ◽  
Nirali M. Patel ◽  
Juneko E. Grilley-Olson ◽  
Xiaobei Zhao ◽  
...  

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.


2018 ◽  
Vol Volume 11 ◽  
pp. 1-11 ◽  
Author(s):  
Chundi Gao ◽  
Huayao Li ◽  
Jing Zhuang ◽  
HongXiu Zhang ◽  
Kejia Wang ◽  
...  

2018 ◽  
Vol 17 (2) ◽  
pp. 476-487 ◽  
Author(s):  
Fengju Chen ◽  
Yiqun Zhang ◽  
Sooryanarayana Varambally ◽  
Chad J. Creighton

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