A systematic comparison of copy number alterations in four types of female cancer

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.

Conjoint analysis of m6A regulators and copy number variations in thyroid carcinoma

“…m6A RNA modi cation affects tumor proliferation [16], differentiation, tumorigenesis, invasion [17], and metastasis [18] by regulating proto-oncogenes and tumor suppressor genes. Similarly, CNVs play a crucial role in the occurrence, development, and outcome of several cancers, such as lung, endometrial, prostate, and gastric cancers [19][20][21][22]. However, the role of m6A methylation modi cation and CNVs in THCA is unknown.…”

Aberrations of the number of copies (CNA) in the genome of luminal B breast tumor

“…Несмотря на тот факт, что опухоли молочной железы имеют высокую степень внутриопухолевой гетерогенности, для них определены наиболее часто встречающиеся хромосомные аберрации. При РМЖ (в том числе и по данным TCGA) высокую частоту встречаемости имеют CNA в 1q, 8q, 8p, 11q, 13q, 16q, 17q и 20q регионах [4][5][6].…”

Sensitive and specific detection of circulating tumor cells promotes precision medicine for cancer

“…In the past, CGH was applied for analysis of tumor tissues, but many studies have suggested that data from primary tumors alone is insufficient. Array CGH, which exploits ordered arrays of genomic DNA sequences, is widely used for analysis of CTCs, including identification of genomic alterations which include insertion/deletion, singlenucleotide variations, copy number variations (CNVs) [72] ; identification of candidate oncogenes or tumor suppressors; identification of novel biomarkers involved in metastasis, cancer progression and therapy response; and identification of subgroups of CTCs [73] . High-throughput NGS is another strong technology to analyze heterogeneity of CTCs and reveal the mechanisms of metastasis, which might be the Achilles' heel in disease progression.…”