Abstract
BackgroundDetection and localization of genomic alterations and breakpoints are crucial in cancer research. The purpose of this study was to investigate, in a methodological and biological perspective, different female, hormone-dependent cancers to identify common and diverse DNA aberrations, genes, and pathways.MethodsIn this work, we analyzed tissue samples from patients with breast (n = 112), ovarian (n = 74), endometrial (n = 84), or cervical (n = 76) cancer. To identify genomic aberrations, the Circular Binary Segmentation (CBS) and Piecewise Constant Fitting (PCF) algorithms were used and segmentation thresholds optimized. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was applied to the segmented data to identify significantly altered regions and the associated genes were analyzed by Ingenuity Pathway Analysis (IPA) to detect over-represented pathways and functions within the identified gene sets.Results and DiscussionAnalyses of high-resolution copy number alterations in four different female cancer types are presented. For appropriately adjusted segmentation parameters the two segmentation algorithms CBS and PCF performed similarly. We identified one region at 8q24.3 with focal aberrations that was altered at significant frequency across all four cancer types. Considering both, broad regions and focal peaks, three additional regions with gains at significant frequency were revealed at 1p21.1, 8p22, and 13q21.33, respectively. Several of these events involve known cancer-related genes, like PPP2R2A, PSCA, PTP4A3, and PTK2. In the female reproductive system (ovarian, endometrial, and cervix [OEC]), we discovered three common events: copy number gains at 5p15.33 and 15q11.2, further a copy number loss at 8p21.2. Interestingly, as many as 75% of the aberrations (75% amplifications and 86% deletions) identified by GISTIC were specific for just one cancer type and represented distinct molecular pathways.ConclusionsOur results disclose that some prominent copy number changes are shared in the four examined female, hormone-dependent cancer whereas others are definitive to specific cancer types.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2899-4) contains supplementary material, which is available to authorized users.
Highlights
Detection and localization of genomic alterations and breakpoints are crucial in cancer research
Our results disclose that some prominent copy number changes are shared in the four examined female, hormone-dependent cancer whereas others are definitive to specific cancer types
Comparing different segmentation algorithms Accurate detection of chromosomal aberrations is crucial for comparing multiple Copy number alteration (CNA) data sets originating from different platforms and cancer types
Summary
Detection and localization of genomic alterations and breakpoints are crucial in cancer research. Kaveh et al BMC Cancer (2016) 16:913 tumor suppressor gene PTEN, located on 10q23, have been reported in various human malignant tumors, including endometrial, ovarian, breast, cervical, and lung cancer [8,9,10] Detection of such aberrations may point to genes that are critical in cancer development and may point to targetable pathways [11]. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm [17] was used to identify regions significantly altered in the different cancer data sets These regions were further analyzed, on both the gene and pathway level, to reveal mechanisms of disease evolution common to multiple female cancer types. These results may bring novel insight into the characteristics of the onset and progression of female cancers and possibly identify some common underlying mechanisms of hormonal influence in the risk of cancer
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