An Integrated Epigenomic and Genomic View on Phyllodes and Phyllodes-like Breast Tumors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE179458 | GEO | 2021/07/07
REPOSITORIES: GEO
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Project description:An Integrated Epigenomic and Genomic View on Phyllodes and Phyllodes-like Breast Tumors
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Project description:Fibroepithelial lesions (FL) of the breast, in particular, phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT and fibroadenomas. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions, and EGFR amplifications may inform therapeutic decision-making.
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Project description:WG-DASL expression of breast fibroepithelial lesions Breast fibroepithelial lesions are biphasic tumors and include fibroadenomas and phyllodes tumors. Fibroadenomas are clinically benign while phyllodes tumors are more unpredictable in biological behavior, with potential for recurrence. Differentiating the tumors may be challeneging when they have overlapping clinical and histological features especially on the core biopsies
2016-04-29 | GSE78071 | GEO
Project description:To investigate the pathogenesis of malignant phyllodes tumors of the breast, we used lncRNA+mRNA microarray expression profiling as a platform to investigate lncRNAs that play a key role in the malignant progression of phyllodes tumors of the breast.A total of 4 cases of breast fibroadenomas, 6 cases of benign phyllodes tumors and 6 cases of malignant phyllodes tumors were included. Fibroadenomas and benign phyllodes tumors were used as controls to screen out significantly differentially expressed lncrnas in malignant phyllodes tumors.
2024-06-20 | GSE235267 | GEO
Project description:Genome wide DNA methylation profiling of phyllodes tumour, fibroadenoma and metaplastic breast cancer samples. The Illumina Infinium Methylation EPIC v1.0 BeadChip Array was used to obtain DNA methylation profiles across approximately 866,000 CpGs from primary tumours. Samples included a range of grades of phyllodes tumours (n=29), fibroadenoma (n=2), and metaplastic breast cancer (n=2).
2023-12-15 | GSE231574 | GEO
Project description:Breast malignant phyllodes tumors (PTs) are rapid-progressing tumors, known to lack effective treatment and suitable prognostic markers as well as elaborate studies. Herein,we found that level of CD146 is progressively elevated with malignant progression of PTs and is an independent predictor for prognosis of PT patients.Mechanistically, CD146 activates the PI3K/AKT signaling pathway, thereby enhancing malignant behaviors of PT cells.This study unveils a CD146-PI3K/AKT axis in modulating the malignant progression of PTs, and open avenues to develop a novel target for precise prognosis and treatment for breast malignant PTs.
2023-12-01 | GSE227380 | GEO
Project description:We generated large-scale proteome data for 65 human breast tumors and 53 paired adjacent non-cancerous tissue and performed an integrated proteotranscriptomic characterization. To our best knowledge, the study is one of the largest quantitative proteomic study of human breast tissues, including the analysis of 118 tissue samples from 65 patients with long-term survival outcomes. Our data show that protein expression describes a tumor biology that is only partly captured by the transcriptome, with mRNA abundance incompletely predicting protein abundance in tumors, and even less so in non-cancerous tissue. Furthermore, the tumor proteome described disease pathways and subgroups that were only partially captured by the tumor transcriptome.
2018-12-04 | PXD005692 | Pride
Project description:The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.
| S-EPMC3906004 | biostudies-literature
Project description:CD146 accelerates malignant progression of phyllodes tumor cells
| PRJNA944931 | ENA
Project description:BackgroundThe genomic landscape of breast malignant phyllodes tumors (PTs) is not well defined, especially pregnancy-related malignant PTs. To clarify this topic, whole-exome next-generation sequencing (NGS) was performed on tumor samples and paired normal breast tissues from two pregnancy-related malignant PTs, followed by a functional analysis of the genetic alterations.MethodsDNA from malignant PT samples and matched normal breast tissues of both patients were subjected to molecular profiling. NGS of the whole-exome was performed in a commercial molecular pathology laboratory. Predictive tools were used to estimate genetic variation in somatic and germline genes.ResultsIn total, 29 somatic genomic alterations and 18 germline alterations were found in both patients. In Patient 1, 12 aberrations were identified in the tumor tissue, and 9 alterations were identified in matched normal breast tissue. One pathogenic variant in tumor suppressor genes (TP53) was detected in patient 1. In Patient 2, 18 and 10 variants were found in the tumor and matched normal breast tissue, respectively. In Patient 2, pathogenic alterations were identified in two tumor suppressor genes (PTEN and TP53). PTEN and TP53 may be potential drug targets. The functional predictive tools showed that genes of unknown significance for PTs, including FCHO1 in Patient 1, and LRP12 and PKM in Patient 2, were pathogenic. Several genes, including FCHO1, LRP12 and PKM, were shown for the first time to be altered in malignant PTs. A potentially pathogenic germline variant in PRF1, was detected in Patient 1.ConclusionOur study first demonstrated somatic and germline gene alterations in two malignant PTs during pregnancy and lactation. These two PTs shared major genetic events, including TP53 mutation, which commonly occurs in malignant PTs; additionally, we identified two potential genes for targeted therapy, TP53 and PTEN. One germline mutation in PRF1 was also detected. These results provide clues regarding tumor pathogenesis and precision therapy development.
| S-EPMC9587670 | biostudies-literature