Combined Analysis of SNP Array Data Identifies Novel CNV Candidates and Pathways in Ependymoma and Mesothelioma

Our plain-English summary of Combined Analysis of SNP Array Data Identifies Novel CNV Candidates and Pathways in Ependymoma and Mesothelioma, by G. Wajnberg, B.S. Carvalho, C.G. Ferreira, et al (BioMed Research International, 2015).

The study

• Authors: G. Wajnberg, B.S. Carvalho, C.G. Ferreira, F. Passetti
• Journal: BioMed Research International
• Published: 2015;2015:902419
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Copy number variation is a class of structural genomic modifications that includes the gain and loss of a specific genomic region, which may include an entire gene. Many studies have used low-resolution techniques to identify regions that are frequently lost or amplified in cancer. Usually, researchers choose to use proprietary or non-open-source software to detect these regions because the graphical interface tends to be easier to use. In this study, we combined two different open-source packages into an innovative strategy to identify novel copy number variations and pathways associated with cancer. We used a mesothelioma and ependymoma published datasets to assess our tool. We detected previously described and novel copy number variations that are associated with cancer chemotherapy resistance. We also identified altered pathways associated with these diseases, like cell adhesion in patients with mesothelioma and negative regulation of glutamatergic synaptic transmission in ependymoma patients. In conclusion, we present a novel strategy using open-source software to identify copy number variations and altered pathways associated with cancer.

In plain English

This was a computer reanalysis of genetic data already published by other research groups, not a new study of patients. The authors ran publicly available SNP array data from matched tumor and blood DNA of 23 mesothelioma patients and 40 intracranial ependymoma patients through two open-source software packages, DNAcopy and CGHcall, to find DNA regions that were gained or lost. The study did not examine asbestos or any other exposure. In the mesothelioma data, DNAcopy found losses on chromosome arm 9p, which contains the CDKN2A and CDKN2B tumor suppressor genes, in 10 patients (43% of cases). Both packages found loss of both copies of the CDH8 gene in 6 patients. A pathway analysis gave a 93% probability that adherens junction organization was affected. In the ependymoma data, the method found 29 of the 33 gained regions and all 5 lost regions that the original researchers had reported. The authors concluded that their results were similar to the original reports but also identified new copy number changes and possibly altered pathways. Some numbers in the article contradict each other.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Computational (bioinformatics) reanalysis of two previously published public SNP array datasets, presented as a new method combining two open-source software packages
• Who was studied: Existing data from matched tumor and peripheral blood DNA samples: 23 mesothelioma patients (GEO GSE20989, from Christensen and colleagues) and 40 intracranial ependymoma patients (GEO GSE32101, from Kilday and colleagues). The type of mesothelioma (pleural or peritoneal) is not stated.
• Main results:
  • Mesothelioma dataset: using DNAcopy, 10 patients had losses on chromosome arm 9p, which includes the CDKN2A and CDKN2B tumor suppressor genes (43% of cases)
  • Mesothelioma dataset: loss of both copies of the CDH8 gene (16q region) in 6 patients, found with both packages
  • Mesothelioma dataset: the Results section states that all 10 lost regions reported by Christensen and colleagues were detected. The Discussion instead says 8 of 11 detected lost arms matched.
  • Mesothelioma dataset: gene set analysis gave adherens junction organization a 93% probability of being affected and the Fanconi anemia pathway 86%
  • Ependymoma dataset: of the 33 amplified regions and 5 lost regions reported by Kilday and colleagues, the authors identified 29 amplified regions with both packages and all 5 lost regions
  • Ependymoma dataset: 1q was the most frequently amplified region (22.5% of patients with DNAcopy), and 2q was lost in 27.5% of patients
  • Ependymoma dataset: negative regulation of glutamatergic synaptic transmission was flagged as altered with a probability of 55%
• The authors' conclusion: The authors concluded that their combined method gave results similar to those originally reported but also identified novel copy number changes and possibly altered pathways, which they suggested could be investigated further as potential drug targets

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chemotherapy.

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