Homo sapiens
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PROVIDER: PRJNA341380 | ENA |
REPOSITORIES: ENA
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Project description:AIMS: HER2 testing of invasive breast cancer by in-situ hybridisation guides therapy decisions. Probing HER2 and cen17 simultaneously is supposed to reveal both a potential HER2 gene amplification and polysomy 17. However, a considerable number of breast cancer patients with quasi polysomy 17 are considered "equivocal" which is diagnostically meaningless. Moreover, patients with equivocal / false polysomic tumours are prevented from a potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122, and TP53 hybridisation markers to reliably indicate true polysomy and to accurately reclassify equivocal samples as HER2-positive. METHODS AND RESULTS: Samples with (n = 82) and without (n = 52) increased cen17 copy numbers and 78 evidently HER2-amplified specimens were analysed using dual and triple marker hybridisation probes. Selected putative polysomic samples were subjected to array-based comparative genomic hybridisation. We found that 37.8% samples with putative polysomy 17 did not show any gain in RAI1, D17S122, or TP53. Accordingly, aCGH revealed evidence for the presence of HER2/cen17 coamplification rather than for true polysomy in those cases. Reflex testing using alternate 17p markers reclassified up to 56.3% equivocal cases as HER2-positive and the combined assessment of a 17p and 17q locus allows the differentiation of true vs. false polysomy. CONCLUSIONS: An increased cen17 copy number does not necessarily reflect polysomy and reflex testing facilitates the reclassification of "equivocals". Nevertheless, the prognostic and predictive value of a HER2/cen17 coamplification versus HER2 gene amplification alone must still be prospectively evaluated. This article is protected by copyright. All rights reserved.
2017-01-01 | GSE86305 | GEO
Project description:Interventions: 64Cu-DOTA labeled antibody probes against HER2 and EGFR
Primary outcome(s): Visualization of PET imaging with 64Cu-DOTA labeled antibody probes against HER2 and EGFR. Comparison between PET imaging and expression of HER2 and EGFR.
Study Design: Single arm Non-randomized
| 2632761 | ecrin-mdr-crc
Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors. Neoadjuvant study of 50 HER2-positive breast cancer cases treated with trastuzumab-based chemotherapy pre-operatively. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to Affymetrix microarrays according to manufacturer protocol. Pathologic response was assessed at the end of neoadjuvant treatment.
2012-05-11 | E-GEOD-37946 | biostudies-arrayexpress
Project description:Background: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between HER2 positive and negative breast cancer tumors remain unclear. Objective: The aim of this study was to identify a gene expression profile for breast tumors based on HER2 status. Material and methods: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. Results: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, as well as other genes located on 17q12, and genes functionally related to migration. Conclusion: Our study shows the potential of integrated genomics profiling to shed light on the molecular knowledge of HER2-positive breast tumors. The tumor samples under study correspond to 54 primary breast carcinomas. They included 15 cases with a HER2 IHC3+ score with HER2 gene amplification, 13 cases with IHC2+ score with amplification and 13 without HER2 gene amplification, and 13 cases IHC0/1+ score without HER2 gene amplification. 12 samples of breast normal tissues from breast cancer patients were also included as a reference. Neither overexpression nor amplification of HER2 was observed.
2011-12-22 | E-GEOD-29431 | biostudies-arrayexpress
Project description:The Formalin-Fixed Paraffin-Embedded (FFPE) samples on selected breast cancer subtypes (ER+/Her2-, ER+/Her2+, ER-/Her2+, and ER-/Her2-) and their paired fresh fine needle aspirated biopsies (FNA) were investigated. The cases represented different subtypes of breast cancers based on their clinical receptors ER (E) and Her2 (H) status to demonstrate the ability of gene profiles to differentiate these tumors. Compared to FNA specimens, FFPE samples yielded relatively more degraded RNA, and 80% of the samples deemed suitable for cDNA-mediated annealing, selection, extension and ligation (DASL) assay. It is able to demonstrate that gene profiles from FFPE microarrays were reproducible and correlated well with the corresponding gene profiles from FNA microarrays. The gene profiles from both FNA and FFPE could differentiate the four breast cancer subtypes, and the expression levels of corresponding gene set were consistent with qRT-PCR and correlated to the clinical outcomes on published microarray data. It supports the use of FFPE specimens to develop a prognostic tool for breast cancers which can obviate the need for fresh specimens. 25 FNA specimens were processed for direct hybridization assays using Illumina Human-Ref8 version 3 BeadChips. Invasive ductal carcinoma (IDC)-type subtypes ER+/Her2-, ER+/Her2+, ER-/Her2+, and ER-/Her2- (ER: estrogen receptor, HER2: human epidermal growth factor receptor 2) were analyzed.
2011-06-22 | E-GEOD-23385 | biostudies-arrayexpress
Project description:The Formalin-Fixed Paraffin-Embedded (FFPE) samples on selected breast cancer subtypes (ER+/Her2-, ER+/Her2+, ER-/Her2+, and ER-/Her2-) and their paired fresh fine needle aspirated biopsies (FNA) were investigated. The cases represented different subtypes of breast cancers based on their clinical receptors ER (E) and Her2 (H) status to demonstrate the ability of gene profiles to differentiate these tumors. Compared to FNA specimens, FFPE samples yielded relatively more degraded RNA, and 80% of the samples deemed suitable for cDNA-mediated annealing, selection, extension and ligation (DASL) assay. It is able to demonstrate that gene profiles from FFPE microarrays were reproducible and correlated well with the corresponding gene profiles from FNA microarrays. The gene profiles from both FNA and FFPE could differentiate the four breast cancer subtypes, and the expression levels of corresponding gene set were consistent with qRT-PCR and correlated to the clinical outcomes on published microarray data. It supports the use of FFPE specimens to develop a prognostic tool for breast cancers which can obviate the need for fresh specimens. 25 FFPE specimens were processed for whole genome DASL assays using Illumina Human-Ref8 version 3 BeadChips. Invasive ductal carcinoma (IDC)-type subtypes ER+/Her2-, ER+/Her2+, ER-/Her2+, and ER-/Her2- (ER: estrogen receptor, HER2: human epidermal growth factor receptor 2) were analyzed.
2011-06-22 | E-GEOD-23384 | biostudies-arrayexpress
Project description:The Epidermal Growth Factor Receptor 2 (ERBB2 or HER2) is amplified and overexpressed in approximately 20% of invasive breast cancers and is associated with metastasis and poor prognosis. Here we describe the role of a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells. Overexpression of Delta-HER2 in human mammary cells decreased apoptosis and increased proliferation and expression of epithelial-to-mesenchymal markers. It also induced invasion in three-dimensional cultures and promoted tumorigenicity and metastasis in vivo. In contrast, similar overexpression of wild-type HER2 failed to evoke the same effects. Unbiased protein-tyrosine phosphorylation profiling revealed a significant increase in phosphorylation of several key signaling proteins upon Delta-HER2 expression, some of which not previously shown to belong to the HER2 pathway. In addition, microarray analysis revealed the expression of a set of genes specifically associated with Delta-HER2 expression. We found those genes to be highly expressed in ER-negative, high grade and metastatic primary breast tumors. Altogether, these results provide new insights into the function of a tumorigenic splice variant of HER2 and the signaling cascade deriving from its activity RNA was extracted from MCF10A expressing empty vector, WT-HER2 or Delta-HER2 (n=3).
2013-10-22 | E-GEOD-42781 | biostudies-arrayexpress
Project description:Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial (ClinicalTrials.gov Identifier: NCT01875666, LCCC1214) designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 transcription factor expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. Patient samples from this trial, when sufficient material was available, were also subjected to kinase enrichment using multiplexed kinase inhibitor bead affinity chromatography and LC-MS/MS. Strongly responsive transcriptional responses observed in a subset of patients corresponded to decreased binding of CDK1 and DDR1 by our proteomic approach. Taken together, our results highlight the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.
2021-04-09 | PXD021865 | Pride
Project description:Background: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore, gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers. Methods: We examined gene expression in 46 cases of microdissected NlEpi from previously untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 ER+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9ER+, 7 ER-), we validated seven selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results: 216 probes (corresponding to 198 unique genes) distinguished the NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers themselves, (e.g., ESR1, GATA3, and CX3CL1, FABP7, respectively). QPCR validated the microarray results in both a sampling of the 30 original cases (84%) and all of the 16 independent cases (77%). Gene expression in NlEpiER+ and NlEPIERNlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 36%-53% of the genes or probes examined in each the 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions: Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. Thus, breast cancer subtypes may be detectable before histologic abnormalities. NlEpi gene expression may help define subtype-specific risk signatures, identify initial subtype specific genomic differences, and suggest new targets for subtype-specific prevention and therapy. We determined that 216 probesets significantly differed between histologically normal epithelium from ER+ breast cancer patients and from ER- breast cancer patients, and that gene expression in each type of histologically normal epithelium resembles expression of the corresponding subtype of invasive breast cancer (i.e., ER+ or ER-). These findings suggest that characteristic features of breast cancer subtypes are detectable prior to any histologic abnormality. This suggestion has implications for understanding breast cancer biology and devising new tools for assessing breast cancer risk.
2010-12-07 | GSE21947 | GEO
Project description:We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. Our results indicate that even driver genetic alterations, such as HER2, can be heterogeneously distributed in a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification.
2015-04-16 | GSE67908 | GEO