Abstract A1-67: Prognostic significance of copy number aberrations in Wilms tumor

Purpose The biologic behavior of intracranial ependymoma is unpredictable on the basis of current staging approaches. We aimed at the identification of recurrent genetic aberrations in ependymoma and evaluated their prognostic significance to develop a molecular staging system that could complement current classification criteria. Patients and Methods As a screening cohort, we studied a cohort of 122 patients with ependymoma before standardized therapy by using array-based comparative genomic hybridization. DNA copy-number aberrations identified as possible prognostic markers were validated in an independent cohort of 170 patients with ependymoma by fluorescence in situ hybridization analysis. Copy-number aberrations were correlated with clinical, histopathologic, and survival data. Results In the screening cohort, age at diagnosis, gain of 1q, and homozygous deletion of CDKN2A comprised the most powerful independent indicators of unfavorable prognosis. In contrast, gains of chromosomes 9, 15q, and 18 and loss of chromosome 6 were associated with excellent survival. On the basis of these findings, we developed a molecular staging system comprised of three genetic risk groups, which was then confirmed in the validation cohort. Likelihood ratio tests and multivariate Cox regression also demonstrated the clear improvement in predictive accuracy after the addition of these novel genetic markers. Conclusion Genomic aberrations in ependymomas are powerful independent markers of disease progression and survival. By adding genetic markers to established clinical and histopathologic variables, outcome prediction can potentially be improved. Because the analyses can be conducted on routine paraffin-embedded material, it will now be possible to prospectively validate these markers in multicenter clinical trials on population-based cohorts.

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Faculty Opinions recommendation of Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1157546.617731 ◽

2009 ◽

Author(s):

Eric Bouffet

Keyword(s):

Copy Number ◽

Outcome Prediction ◽

Dna Copy Number ◽

Copy Number Aberrations ◽

Pediatric Medulloblastoma ◽

Dna Copy Number Aberrations

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Faculty Opinions recommendation of Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718042729.793480784 ◽

2013 ◽

Author(s):

Gerardo Ferrara ◽

Anna Chiara De Vanna

Keyword(s):

Risk Assessment ◽

Copy Number ◽

Copy Number Aberrations ◽

Chromosomal Copy Number ◽

Chromosomal Copy

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Wilms tumor 1 gene expression in acute myeloid leukemia: Prognostic significance and usefulness in minimal residual disease monitoring.

ALEXMED ePosters ◽

10.21608/alexpo.2020.43157.1037 ◽

2020 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Nada El Sweify

Keyword(s):

Gene Expression ◽

Myeloid Leukemia ◽

Residual Disease ◽

Wilms Tumor ◽

Prognostic Significance ◽

Disease Monitoring ◽

Minimal Residual Disease Monitoring ◽

Wilms Tumor 1 ◽

Minimal Residual ◽

Acute Myeloid

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Characterization of fragment sizes, copy number aberrations and 4‐mer end motifs in cell‐free DNA of hepatocellular carcinoma for enhanced liquid biopsy‐based cancer detection

Molecular Oncology ◽

10.1002/1878-0261.13041 ◽

2021 ◽

Author(s):

Chao Jin ◽

Xiaonan Liu ◽

Wenyuan Zheng ◽

Liping Su ◽

Yang Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Detection ◽

Liquid Biopsy ◽

Copy Number ◽

Cell Free Dna ◽

Copy Number Aberrations ◽

Free Dna

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An Unusual Case of Desmoplastic Melanoma With Monster Cells Imitating an Atypical Fibroxanthoma

International Journal of Surgical Pathology ◽

10.1177/10668969211044758 ◽

2021 ◽

pp. 106689692110447

Author(s):

Juan J. Ríos-Martín ◽

Manuel Pérez-Pérez ◽

Sebastián Umbría-Jiménez ◽

David Moreno-Ramírez ◽

Ana Vallejo-Benítez

Keyword(s):

Cyclin D1 ◽

Copy Number ◽

Poor Prognosis ◽

Unusual Case ◽

Prognostic Significance ◽

Mutation Status ◽

Atypical Fibroxanthoma ◽

Desmoplastic Melanoma ◽

Aggressive Tumor

Numerous cells with very large and irregular nuclei (“monster” cells) have not hitherto been reported in desmoplastic melanoma (DM). Their prognostic significance in melanomas is a matter of debate, although some authors have associated them with more aggressive tumor behavior. We report a mixed DM on the scalp of an 88-year-old woman imitating an atypical fibroxanthoma. Tumor cells stained positive for SOX10, S100, and cyclin D1; BRAF mutation status was negative, and fluorescence in situ hybridization analysis showed copy number gains in 11q13 (cyclin D1) and 6p25 (RREB1), and loss in 6q23 (MYB). Cyclin D1 amplification is associated with poor prognosis in melanoma.

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Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations

10.1101/278887 ◽

2018 ◽

Author(s):

An-Shun Tai ◽

Chien-Hua Peng ◽

Shih-Chi Peng ◽

Wen-Ping Hsieh

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Copy Number ◽

Tumor Heterogeneity ◽

Tumor Evolution ◽

Depth Information ◽

Sequencing Data ◽

Single Nucleotide Variants ◽

Copy Number Aberrations

AbstractMultistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.

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