Abstract 661: Identification of epigenomic markers on chromosome 11 that distinguish between choroid plexus carcinoma (CPC) and papilloma (CPP).
Bibliographic record
Abstract
Abstract Choroid plexus tumors are rare epithelial brain tumors occurring predominantly in early childhood. Understanding molecular events leading to development and progression of these tumors is critical in determining patient treatment and increased survival. Loss of heterozygosity (LOH) is a common alteration observed during carcinogenesis. To investigate somatic genetic abnormalities in different subtypes of choroid plexus cancers and identify LOH hotspots, we utilized SNP 6.0 arrays (Affymetrix). Allele specific copy number analysis of 25 CPCs and 31 CPPs using Chromosome Analysis Suite (Affymetrix) revealed much higher frequency of LOH events throughout the genome in CPCs (8.4/case) compared with CPPs (1.2/case). One LOH hotspot, neutral copy loss of heterozygosity on chromosome 11, was identified in most CPCs but in no CPPs. Chromosome 11 is known to harbor an imprinted cluster that has been associated with growth dysregulation and pediatric cancer. Both maternal (KvDMR1) and paternal (H19DMR) differentially methylated regions overlap this imprinting cluster. Therefore, we investigated whether the observed LOH is related to uniparental disomy (UPD). Bisulfite pyrosequencing on a subset of CPP and CPC were studied for DNA methylation at both H19DMR and KvDMR1. Our data showed a reverse correlation in the degree of DNA methylation between the 2 DMRs in CPCs and CPPs. These data correlate well with the concept of UPD identified through our SNP arrays. Next, we investigated whether the observed higher expression of insulin like growth factor (IGF2) in CPP compared to CPC is associated with DNA methylation aberrations at the imprinted control region (H19 DMR) on 11p15.5. We identified higher DNA methylation at the H19DMR in CPC compared to CPP. Increased activity of the IGF2 gene has been associated with many types of cancer. To investigate the mechanism of CPC distinct IGF2 expression we examined the expression levels of microRNAs (miRNAs). MicroRNAs are often found to be misregulated in human cancer, and they can act posttranscriptionally as either potent oncogenes or tumor suppressor genes. We studied expression of miR-675-3p, miR-483-3p as well as miR-125-a-3p associated with IGF2/H19 imprinted locus. By quantitative RT-PCR, both miR-675 and miR-125 were found to be more significantly upregulated in CPCs than in CPPs whereas miR-483 was expressed at very low levels in CPCs and in higher levels in CPPs compared with normal control tissues . Misregulation of miR-483 was positively correlated with IGF2 levels in both groups. Our data suggest that dysregulation of epigenetic mechanisms contribute to the molecular events leading to tumor development and progression in CPC and may eventually facilitate identification of new diagnostic markers for CPC, as well as new therapeutic targets for this aggressive, lethal tumor. Citation Format: Malgorzata Pienkowska, Sanaa Choufani, Boleslaw Lach, Diana M. Merino, Ana Novokmet, Uri Tabori, Richard Gilbertson, David Malkin. Identification of epigenomic markers on chromosome 11 that distinguish between choroid plexus carcinoma (CPC) and papilloma (CPP). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 661. doi:10.1158/1538-7445.AM2013-661
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".