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Status |
Public on Oct 01, 2019 |
Title |
Global surveillance of somatic alterations in triple negative breast cancers by whole exon sequencing analyses |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Triple negative breast cancers (TNBC), defined by lacking the expression of oestrogen receptor-alpha (ERa), progesterone receptor, and HER2, is considered to be one of the most aggressive subtypes of all breast cancers. To elucidate the genomic and molecular aberrations in TNBC, we performed whole exon sequencing (WES) analysis on 36 TNBC, and identified 117 genes that significantly mutated (q < 0.05) in TNBC including MUC4, MUC6, TP53, and PIK3CA. Interestingly, genes associated with chromatin regulators including the subunits of SWI/SNF complex were frequently mutated in 44.7% of the cases. Furthermore, from the aspect of the possible association of epigenetic dysregulation and TNBC carcinogenesis, we focused on epigenome and genetic alterations of SALL3, an intrinsic inhibitor of DNMT3A, and identified the role of its dysfunction on cancer cell growth. Our study suggests that epigenetic aberrations caused by somatic alterations including DNA methylation might be a potential pathogenesis of TNBC in a certain number of cases.
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Overall design |
Human TNBC cell line, BT-20, was seeded at a density of 2.5x10^5 cells per 3.5 cm dish. Cells were transfected with 50nM siRNA (siEGFP or siSALL3) by Lipofectamine RNAiMAX reagent. Total RNA was extracted 48h and 96h after transfection. 100 ng of total RNA from each sample was amplified using T7 RNA polymerase with simultaneous Cy3-labeled CTP incorporation. Then, 2 μg of Cy3-labeled cRNA was fragmented, and hybridized onto the Agilent Whole Human Genome Microarray 8x60K slide. Then, a slide was scanned by the Agilent Microarray scanner system. The data were analyzed using GeneSpring. We identified up- and down-regulated genes common to siSALL3_48h and siSALL3_96h compared with siEGFP_48h. The fold change was >2.0.
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Contributor(s) |
Matsushita Y, Komatsu M, Kiyotani K, Yoshimaru T, Katagiri T |
Citation missing |
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Submission date |
Sep 29, 2016 |
Last update date |
Oct 02, 2019 |
Contact name |
Yosuke Matsushita |
E-mail(s) |
y-matsushita@genome.tokushima-u.ac.jp
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Organization name |
Tokushima University
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Department |
Institute for Genome Research
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Lab |
Division of Genome Medicine
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Street address |
3-18-15 Kuramoto
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City |
Tokushima |
ZIP/Postal code |
770-8503 |
Country |
Japan |
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Platforms (1) |
GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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Samples (8)
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Relations |
BioProject |
PRJNA344888 |