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Article

Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes

Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, Via S. Sofia 89-97, 95123 Catania, Italy
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Academic Editor: Michael Dean
Cancers 2021, 13(7), 1585; https://doi.org/10.3390/cancers13071585
Received: 17 February 2021 / Revised: 21 March 2021 / Accepted: 24 March 2021 / Published: 30 March 2021
(This article belongs to the Special Issue Inside Cancer Genomics: From Structure to Therapy)
Classical cytogenetic studies in breast cancer have identified frequent chromosomal aberrations that produce an increased gene copy number in chromosome 1q (1q-gain) and/or a decreased gene copy number in 16q (16q-loss). The understanding of the contribution of such copy number changes to the genesis and progression of cancer is of paramount importance for the design of cancer models and targeted therapies. We exploited molecular data provided by The Cancer Genome Atlas (TCGA) project in order to form different groups of breast cancers bearing 1q-gain and/or 16q-loss or devoid of such aberrations (1,16-chromogroups). An analysis of differential gene expression among 1,16-chromogroups guided the identification of transcriptionally dysregulated 1q and 16q genes. Pathway analysis revealed functional interactions that shed light on novel molecular targets for subtype-specific cancer therapy.
Derivative chromosome der(1;16), isochromosome 1q, and deleted 16q—producing arm-level 1q-gain and/or 16q-loss—are recurrent cytogenetic abnormalities in breast cancer, but their exact role in determining the malignant phenotype is still largely unknown. We exploited The Cancer Genome Atlas (TCGA) data to generate and analyze groups of breast invasive carcinomas, called 1,16-chromogroups, that are characterized by a pattern of arm-level somatic copy number aberrations congruent with known cytogenetic aberrations of chromosome 1 and 16. Substantial differences were found among 1,16-chromogroups in terms of other chromosomal aberrations, aneuploidy scores, transcriptomic data, single-point mutations, histotypes, and molecular subtypes. Breast cancers with a co-occurrence of 1q-gain and 16q-loss can be distinguished in a “low aneuploidy score” group, congruent to der(1;16), and a “high aneuploidy score” group, congruent to the co-occurrence of isochromosome 1q and deleted 16q. Another three groups are formed by cancers showing separately 1q-gain or 16q-loss or no aberrations of 1q and 16q. Transcriptome comparisons among the 1,16-chromogroups, integrated with functional pathway analysis, suggested the cooperation of overexpressed 1q genes and underexpressed 16q genes in the genesis of both ductal and lobular carcinomas, thus highlighting the putative role of genes encoding gamma-secretase subunits (APH1A, PSEN2, and NCSTN) and Wnt enhanceosome components (BCL9 and PYGO2) in 1q, and the glycoprotein E-cadherin (CDH1), the E3 ubiquitin-protein ligase WWP2, the deubiquitinating enzyme CYLD, and the transcription factor CBFB in 16q. The analysis of 1,16-chromogroups is a strategy with far-reaching implications for the selection of cancer cell models and novel experimental therapies. View Full-Text
Keywords: chromosome aberrations; cancer aneuploidy; gene copy number abnormalities; breast cancer; transcriptome; cancer genomics; BCL9; CDH1; gamma-secretase; cancer driver genes chromosome aberrations; cancer aneuploidy; gene copy number abnormalities; breast cancer; transcriptome; cancer genomics; BCL9; CDH1; gamma-secretase; cancer driver genes
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    Description: Figure S1: schematic workflow of analysis performed in the study. Figure S2: The Normalized Chromosomal Distribution Index (NCDI) of 1q-OverT and 16q-UnderT calculated for each cyto-genetic band of a single chromosome arm. Figure S3: Values of the “modified linear FCvsCTRL” for some representative genes belonging to cluster 1, 3 and 4. Figure S4: Oncoplot showing point mutations detected by WES in 645 samples out of 709 ductal and 149 lobular BRCA samples ana-lysed in TCGA study. Figure S5: Oncoplots showing point mutations detected by WES in 1,16-chromogroups. Table S1: Number samples of SNP-arrays RNAseq and WES analysis, Table S2: 1q-OverUpT in all 1,16-chromogroups, Table S3: 16q-UnderT in all 1,16-chromogroups, Table S4: Metascape_result, Table S5: Analysis I and II GSEA Real Values, Table S6: Analysis I and II GSEA ABS values, Table S7: LvsD DEGs.
MDPI and ACS Style

Privitera, A.P.; Barresi, V.; Condorelli, D.F. Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes. Cancers 2021, 13, 1585. https://doi.org/10.3390/cancers13071585

AMA Style

Privitera AP, Barresi V, Condorelli DF. Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes. Cancers. 2021; 13(7):1585. https://doi.org/10.3390/cancers13071585

Chicago/Turabian Style

Privitera, Anna Provvidenza, Vincenza Barresi, and Daniele Filippo Condorelli. 2021. "Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes" Cancers 13, no. 7: 1585. https://doi.org/10.3390/cancers13071585

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