ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2015
Impact of centralization on aCGH-based genomic profiles for precision medicine in oncology.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors.Nature genetics · 2018Article
- Custom Array Comparative Genomic Hybridization: the Importance of DNA Quality, an Expert Eye, and Variant Validation.International journal of molecular sciences · 2017Article
- rCGH: a comprehensive array-based genomic profile platform for precision medicine.Bioinformatics (Oxford, England) · 2016Article
- Intra-tumor genetic heterogeneity in rectal cancer.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- Early objective response may not be a prognostic factor of survival for patients with metastatic urothelial carcinoma: from a retrospective analysis of a cohort of 113 patients.Journal of negative results in biomedicine · 2015Article
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Authors and funding
6 authors.
Funding
Abstract
backgroundComparative genomic hybridization (CGH) arrays are increasingly used in personalized medicine programs to identify gene copy number aberrations (CNAs) that may be used to guide clinical decisions made during molecular tumor boards. However, analytical processes such as the centralization step may profoundly affect CGH array results and therefore may adversely affect outcomes in the precision medicine context. PATIENTS AND
methodsThe effect of three different centralization methods: median, maximum peak, alternative peak, were evaluated on three datasets: (i) the NCI60 cell lines panel, (ii) the Cancer Cell Line Encyclopedia (CCLE) panel, and (iii) the patients enrolled in prospective molecular screening trials (SAFIR-01 n = 283, MOSCATO-01 n = 309), and compared with karyotyping, drug sensitivity, and patient-drug matching, respectively.
resultsUsing the NCI60 cell lines panel, the profiles generated by the alternative peak method were significantly closer to the cell karyotypes than those generated by the other centralization strategies (P < 0.05). Using the CCLE dataset, selected genes (ERBB2, EGFR) were better or equally correlated to the IC50 of their companion drug (lapatinib, erlotinib), when applying the alternative centralization. Finally, focusing on 24 actionable genes, we observed as many as 7.1% (SAFIR-01) and 6.8% (MOSCATO-01) of patients originally not oriented to a specific treatment, but who could have been proposed a treatment based on the alternative peak centralization method.
conclusionThe centralization method substantially affects the call detection of CGH profiles and may thus impact precision medicine approaches. Among the three methods described, the alternative peak method addresses limitations associated with existing approaches.
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