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  • 1
    In: BMC Research Notes, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2011-12)
    Type of Medium: Online Resource
    ISSN: 1756-0500
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2011
    detail.hit.zdb_id: 2413336-X
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  • 2
    Online Resource
    Online Resource
    Bioscientifica ; 2006
    In:  Endocrine-Related Cancer Vol. 13, No. 4 ( 2006-12), p. 1017-1031
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 13, No. 4 ( 2006-12), p. 1017-1031
    Abstract: Molecular profiling for classification and prognostic purposes has demonstrated that the genetic signatures of tumors contain information regarding biological properties as well as clinical behavior. This review highlights the progress that has been made in the field of gene expression profiling of human breast cancer. Breast cancer has become one of the most intensely studied human malignancies in the genomic era; several hundred papers over the last few years have investigated various clinical and biological aspects of human breast cancer using high-throughput molecular profiling techniques. Given the grossly heterogeneous nature of the disease and the lack of robust conventional markers for disease prediction, prognosis, and response to treatment, the notion that a transcriptional profile comprising multiple genes, rather than any single gene or other parameter, will be more predictive of tumor behavior is both appealing and reasonable. Promising results have emerged from these studies, correlating gene expression profiles with prognosis, recurrence, metastatic potential, therapeutic response, as well as biological and functional aspects of the disease. Clearly, the integration of genomic approaches into the clinic lies in the near future, but prospective studies based on larger patient cohorts representing the whole spectrum of breast cancer, oncogenic pathway-based studies, attendant care in bioinformatic analyses and validation studies are needed before the full promise of gene expression profiling can be realized in the clinical setting.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2006
    detail.hit.zdb_id: 2010895-3
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3386-3386
    Abstract: Background: Breast cancer molecular subtypes preferentially metastasize to specific organs, but the underlying molecular mechanisms are not well understood. While several studies have attempted to delineate these mechanisms by making predictions from primary tumours, the likelihood of missing further relevant biological differences which may be enriched or distinctively present in the metastases cannot be overlooked. In addition, survival after relapse is influenced by the anatomical location of the metastasis, with visceral involvement associated with the poorest survival, suggesting that differences in biology and response to treatment may exist. However, the scarcity of clinical material from metastatic lesions has largely prevented detailed molecular characterization of breast cancer site-specific metastases. Material and Methods: We performed global gene expression profiling on 122 fine needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of chemotherapy for metastatic breast cancer. Sub-classification was performed using unsupervised hierarchical clustering, while differentially expressed genes and modulated pathways in metastases from different sites and sub-classes were identified using Significance Analysis of Microarrays (SAM) analysis. Breast cancer survival after relapse was also compared between patients. Results: We confirmed the observation that breast cancer metastasis to visceral organs is associated with the poorest outcome. Molecularly, samples were sub-classified into groups with strong correlations with the previously described breast cancer intrinsic subtypes and also striking overlap with pathological characteristics of the primary tumour. Metastasis pairs from the same individual were more similar to each other than to independent metastatic lesions from other patients. More interestingly, liver metastases formed a unique sub-cluster which could be distinguished from the other sites by the expression of several genes (and pathways) involved in focal adhesion, matrix remodelling, and wnt signalling. Conclusions: Our data suggest that breast cancer molecular subtypes and primary tumour characteristics are to a large extent maintained in recurrences and further that liver metastases may be notably different and represent a distinct entity with a separate underlying biology which may hence require specific targeted therapeutic management. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3386. doi:1538-7445.AM2012-3386
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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    detail.hit.zdb_id: 410466-3
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. P6-08-03-P6-08-03
    Abstract: Background: The site of relapse is associated with the prognosis of metastatic breast cancer, but our understanding of the molecular determinants of organ-specificity of metastasis is incomplete. This study aimed to provide additional insight into the biology of breast cancer liver metastases and to identify liver metastasis-selective genes associated with outcome in primary breast cancer. Methods: A cohort of 304 women with locally advanced and metastatic breast cancer was studied. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 expression were quantified in primary tumors (N=217) by immunohistochemistry and in situ hybridization on tissue microarrays, and molecular subtypes were assigned according to the 2013 St Gallen guidelines. In addition, fine-needle aspirates of metastases (N=91) were subjected to whole genome transcriptional profiling. Results: Liver relapse was significantly associated with ER positivity (P & lt;0.002) and the luminal B-like subtype (P & lt;0.01) and was prognostic of an inferior post-relapse survival (P & lt;0.001). Transcriptional profiling revealed that the major variation in the transcriptional landscape of breast cancer metastases was associated with the expression of hormone receptors and the tumor molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by down-regulation of extracellular matrix (i.e. stromal) genes involved in adhesion and skeletal development. Importantly, we identified a subset of 17 liver metastasis-selective genes that displayed significantly decreased expression in primary tumors of high histological grade (grade 3) and of the luminal B and basal subtypes (P & lt;0.001). This 17-gene signature was significantly and independently prognostic of shorter relapse-free (P =0.001) and overall (P=0.03) survival among patients with ER positive primary tumors. Remarkably, the 17-gene signature remained an independent predictor of shorter relapse-free survival (P=0.004) among patients with luminal A primary tumors. Conclusion: These results highlight a possible role of stroma-related genes in breast cancer liver metastasis biology and validate the prognostic relevance of extracellular matrix/stromal genes in hormone receptor positive primary breast cancer, specifically of the luminal A subtype. Citation Format: Siker Kimbung, Ida Johansson, Anna Danielsson, Srinivas Veerla, Suzanne Egyhazi, Jonas Bergh, Zakaria Einbeigi, Barbro Linderholm, Elisabet Lidbrink, Niklas Loman, Per Malmström, Martin Söderberg, Thomas M Walz, Mårten Fernö, Thomas Hatschek, Ingrid Hedenfalk, the TEX Study Group. Transcriptional profiling of breast cancer metastases identifies liver metastasis-selective genes associated with adverse outcome in luminal A primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 801-801
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 801-801
    Abstract: Male breast cancer (MBC) is a rare disease, accounting for & lt;1% of all breast cancer cases. Although it shares many similarities with female breast cancer (FBC), distinct differences in age distribution, levels of hormone receptors, prognosis, as well as on the transcriptional and genomic levels, have been reported. Due to the rarity of the disease, no large comprehensive studies of the etiology of the disease or randomized trials for optimizing patient management have been conducted. Thus, recommendations for managing MBC are extrapolated from prior knowledge and guidelines for FBC. The aim of this study was to identify candidate driver genes and distinguish them from passenger genes in MBC, an approach that has not been comprehensively explored before. We further compared the landscape of candidate drivers between MBC and FBC, to determine similarities/differences. To this end, we used the computational framework CONEXIC that integrates array-based comparative genomic hybridization (aCGH) data and gene expression (GEX) data for detecting candidate driver genes. Two datasets with matched aCGH and GEX data were used; one containing 53 MBC tumors and the other containing 359 FBC tumors. Male and female breast cancers displayed different landscapes of candidate drivers. We correctly identified many of the known drivers for breast cancer and other types of cancer in the FBC dataset (e.g. GATA3, CCNE1, CDK4, GRB7); however these were not replicated among the MBC tumors. Additionally, we identified novel candidate drivers for breast cancer within both the MBC and FBC datasets. When candidate drivers were investigated separately in the intrinsic subgroups of FBC, differences in the landscapes of drivers were observed, with only a few genes overlapping across the subgroups. Interestingly, Rho GTPase activating protein 30, ARHGAP30, was ranked as a top candidate driver for the HER2 and basal FBC subgroups, as well as for MBC. In fact, this was the only candidate driver gene shared between female and male breast cancers. ARHGAP30 binds to the GTPases RhoU/Wrch-1 and overexpression of RhoU is required for migration. The finding that MBC shares a candidate driver gene with the estrogen receptor (ER) negative HER2 and basal FBC subgroups is surprising, given that the majority of the MBC tumors are ER positive. In summary, the combination of aCGH and GEX data revealed novel candidate driver genes among MBCs, as well as vast differences in the landscapes of candidate drivers between male and female breast cancers. Consequently, the pathobiology of MBC may be very distinct from that of FBC, and men diagnosed with breast cancer may hence require different management and treatment strategies than women. Citation Format: Ida Johansson, Markus Ringnér, Ingrid Hedenfalk. The landscape of candidate driver genes differs between male and female breast cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 801. doi:10.1158/1538-7445.AM2013-801
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 65, No. 21 ( 2005-11-01), p. 9727-9734
    Abstract: Cell cycle deregulation is a prerequisite in tumor development and overexpression of cyclin E, a major G1-S regulator, is often observed in breast cancer and is further linked to poor prognosis. By overexpressing cyclin E in a retinoblastoma-inactivated breast cancer cell line, we induced significant alterations in the expression of genes associated with proliferation and cell adhesion. Rearrangements of the actin cytoskeleton in addition to increased adhesive properties, decreased motility, and invasive potential in functional assays, indicated an overall abrogated mobility. Consistent in vivo findings were obtained upon investigation of 985 primary breast cancers, where cyclin E–high tumors predominantly (67%) displayed a low infiltrative, pushing growth pattern. Furthermore, medullary breast cancers, a subtype defined by its pushing, delimited growth, exhibited a remarkable frequency of cyclin E deregulation (87%) compared with other histologic subtypes (5-20%). Taken together, our results suggest the novel role of cyclin E in modeling infiltrative behavior. The consequences of cyclin E overexpression in breast cancer seems to be multiple, including effects on proliferation as well as growth patterns, a scenario that is indeed observed in the archetype of cyclin E–overexpressing medullary breast cancers.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. S6-05-S6-05
    Abstract: Intro: Male BC is a rare disease ( & lt;1% male tumors); knowledge is limited and management extrapolated from female BC. An international consortium, coordinated by EORTC and TBCRC, was created to better characterize and manage this disease, with 3 parts: 1) retrospective joint analysis 2) prospective registry 3) clinical trial(s). We report 1st results of part 1. Methods: Joint analysis of male BC pts with available FU & FFPE samples, treated in 1990-2010, in 23 centers from 9 countries. Clinical data, long term outcomes, local pathology were centrally analyzed at EORTC. FFPE samples were analyzed at 3 central labs (UK, NL, US) for histology, grade, ER, PR, AR, HER-2, Ki67. Cut-off for positivity: Allred score ≥ 3 for ER/ AR/PR; 20% for Ki67; ASCO-CAP for HER2. Outcome data (OS & RFS) analyzed per Kaplan Meier, p-values correspond to logrank test, CI’s by Brookmeyer & Crowley. Reported % use number of non-missing values as denominator. Results: 1822 pts enrolled; 349 (19%) ineligible (no valid central lab assessment); of 1473 eligible pts (1384 from EU, 89 from US) 63% diagnosed in 2001-2010. Median age at diagnosis (Dx) was 68.5 ys. Of pts with known M status at Dx, 56 (5.1%) were M1; of 1046 M0 cases, 60% were N0 and 51% had T1 tumors at Dx; 4% of pts had BCS and 18% had SLNB; half received adjuvant RT. (Neo)adjuvant CT was used in 30% of M0 pts, most (44%) anthracycline-only; 77% of M0 pts received adjuvant ET, most tamoxifen (88.4%). Central pathology: 697 cases with central histology & grade (full series ongoing): 87% ductal, 53% grade 2. In 1473 pts, at least 1 biomarker centrally assessed; 92% ER highly+ (Allred 7-8), PR had wider variation (35% highly+); 87% AR highly+; 25% Ki67 high; 5% HER2pos. Using IHC surrogates: 58% Luminal A-like, 35% LuminalB-like/HER2neg, 6% LuminalB-like/HER2pos; 0.1% HER2pos/non-Luminal; 1% TNBC (16% not classified). Outcome: For 1046 M0 pts, median FU was 5.7 yrs (0-19.2); 63% alive at analysis; in 88% cause of death was reported, mainly 33% non-cancer and 28% progression(PD)/toxicity. Significant OS improvement over time is seen. 75% (42/56) M1 pts died, mainly due PD. In M0 pts, median OS (yrs) was significantly correlated with ER+ p=0.001 [Allred 0-2: 3.9 (0.1, 6.0); 3-6: 7.1 (4.7, 11.7); 7-8: 8.8 (8.3, 10.0)] & with PR+ p=0.022 [Allred 0-2: 7.3 (6.1, 10.3), 3-6: 8.0 (7.0, 9.3), 7-8: 9.5 (8.4, 12.8)]; less correlation for AR; no major differences for HER2 or Ki67. Median OS & grade (394 cases; full series ongoing): Grade1: 12.8 yrs (6.1-15.6); Grade2: 7.9 (6.5-10.7); Grade3: 9.3 (4.9-21.1). Median OS for IHC surrogates: 8.7 (7.8-9.7) for Luminal A; 8.3 (6.9-9.4) for Luminal B/HER-2neg; 9.3 years (5.9-21.1) for Luminal B/HER-2+. Similar results were seen for RFS. ER/PR/AR using histoscores will be presented. Conclusions: a) 56% pts had T1 tumors at Dx but only 4% had BCS; b) ER was highly + in & gt;90% but adjuvant ET given in only 77% pts; c) Male BC is usually ER+, PR+ & AR+ and of Luminal A-like subtype (5% HER2pos & 1% TNBC); d) Significant improvement in OS over time; e) ER and PR (Allred) are prognostic (high expression/better prognosis), less for AR, not for Ki67 nor IHC surrogates; f) In-depth characterization of samples is ongoing. Funding: BCRF, EBCC Council, Pink Ribbon NL, BRO. Citation Format: Fatima Cardoso, John Bartlett, Leen Slaets, Carolien van Deurzen, Elise van Leewen-Stok, Peggy Porter, Barbro Linderholm, Ingrid Hedenfalk, Carolien Schroder, John Martens, Jane Bayani, Christi van Asperen, Melissa Murray, Clifford Hudis, Lavinia Middleton, Joanna Vermeij, Stephanie Peeters, Judith Fraser, Monica Nowaczyk, Isabel Rubio, Stefan Aebi, Catherine Kelly, Kathryn Ruddy, Eric Winer, Cecilia Nilsson, Lissandra Dal Lago, Larissa Korde, Kim Benstead, Danielle Van Den Weyngaert, Oliver Bogler, Theodora Goulioti, Nicolas Dif, Carlo Messina, Konstantinos Tryfonidis, Jan Bogaerts, Sharon Giordano. Characterization of male breast cancer: First results of the EORTC10085/TBCRC/BIG/NABCG International Male BC Program [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S6-05.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 22, No. 2_Supplement ( 2016-01-15), p. B12-B12
    Abstract: Objective: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype. Despite relatively clear clinical features, OCCCs can be difficult to distinguish morphologically from other epithelial ovarian cancers. OCCC gene expression signatures capturing not only the morphology but also the biology of this tumor subtype have been described, and a previous study using comparative genomic hybridization showed that OCCCs are indeed heterogeneous. Still, only a few genes have been analyzed using gene sequencing techniques. In the present study we aimed to further characterize OCCCs and their histotype specific genetic changes using targeted sequencing of 60 well-established cancer genes. Increased knowledge about genetic aberrations in OCCCs may help to guide future development of targeted treatments and improve the outcome for these patients. Methods: Formalin fixed, paraffin-embedded (FFPE) tumor tissue was collected from 11 primary OCCCs, diagnosed at the Skane University Hospital, Lund, Sweden (1998-2013). One sample was excluded due to poor DNA quality. For the remaining 10 samples, 600 ng genomic DNA/sample was used for single strand targeted DNA sequencing using the SureSeq™ solid tumor panel consisting of 60 key genes involved in cancer evolution, including ovarian cancer. The panel covers all coding exons in the included genes, and is validated for research use on FFPE samples. The publicly available ENSEMBL database was used to classify the mutations according to severity across the genes. Serious mutations, defined as major non-conservative amino acid changes, splice or frameshift variants or changes in stop codons, affecting single nucleotide variations (SNVs) or insertions or deletions of DNA bases (indels) were used for further analyses. The mutation call cut-off was set to 20% and the reading depth ≥300x, and unsupervised hierarchical clustering of the tumor samples was performed. Results: & gt;99% of the target bases had a 30x coverage across all samples, and the mean target coverage was 534x. Using the 20% cut-off, approximately 300 mutations were detected in the 60 genes across the 10 tumor samples. Unsupervised hierarchical clustering revealed two distinct clusters related to mutational load. Mutations in genes previously reported to be affected in OCCCs, such as ARID1A and ERBB2, were identified. Whereas ARID1A was mainly affected in one cluster, mutations in genes signifying a highly malignant phenotype, such as BRCA1 and BRCA2 dominated in the other. Genes in signaling pathways often affected in malignant tumors, as e.g. the RAS pathway, however, were unaffected. Other mutations detected in this dataset were ZFHX3 and KMT2C. KMT2C was the only highly mutated gene across both clusters. The clustering pattern was not related to age of FFPE blocks or tumor cell content. Conclusions: In the present study we show that OCCCs are genetically heterogeneous. The variation in mutation rate is in line with a previous publication, and points to differences in tumor biology that may be important for tumor behavior and thus patient outcome. The highly mutated genes may help in guiding trials of targeted treatments; the methyl transferase gene KMT2C, also known as MLL3, may potentially be one such target. Rearrangements of this gene are well-described in acute leukemias. Interestingly, KMT2C/MLL3 is also reported to be a mutational cancer driver gene in renal clear cell carcinomas according to the TCGA. Likewise, ZFHX3 has recently been reported in endometrial clear cell carcinomas. Despite the small size of this study it points to the well-established fact that ovarian cancer is not one single disease, and also confirms that even the rare OCCCs seem to harbor different biological features which may be of potential clinical importance. Citation Format: Jenny-Maria Jönsson, Nicolai Skovbjerg Arildsen, Anna Ebbesson, Sofia Westbom-Fremer, Anna Måsbäck, Susanne Malander, Mef Nilbert, Ingrid Hedenfalk. Targeted sequencing of ovarian clear cell carcinomas reveals intertumor heterogeneity and distinct clustering related to mutational load. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B12.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 9
    In: BMC Molecular Biology, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2007-12)
    Abstract: Assessing RNA quality is essential for gene expression analysis, as the inclusion of degraded samples may influence the interpretation of expression levels in relation to biological and/or clinical parameters. RNA quality can be analyzed by agarose gel electrophoresis, UV spectrophotometer, or microcapillary electrophoresis traces, and can furthermore be evaluated using different methods. No generally accepted recommendations exist for which technique or evaluation method is the best choice. The aim of the present study was to use microcapillary electrophoresis traces from the Bioanalyzer to compare three methods for evaluating RNA quality in 24 fresh frozen invasive breast cancer tissues: 1) Manual method = subjective evaluation of the electropherogram, 2) Ratio Method = the ratio between the 28S and 18S peaks, and 3) RNA integrity number (RIN) method = objective evaluation of the electropherogram. The results were also related to gene expression profiling analyses using 27K oligonucleotide microarrays, unsupervised hierarchical clustering analysis and ontological mapping. Results Comparing the methods pair-wise, Manual vs . Ratio showed concordance (good vs . degraded RNA) in 20/24, Manual vs . RIN in 23/24, and Ratio vs . RIN in 21/24 samples. All three methods were concordant in 20/24 samples. The comparison between RNA quality and gene expression analysis showed that pieces from the same tumor and with good RNA quality clustered together in most cases, whereas those with poor quality often clustered apart. The number of samples clustering in an unexpected manner was lower for the Manual (n = 1) and RIN methods (n = 2) as compared to the Ratio method (n = 5). Assigning the data into two groups, RIN ≥ 6 or RIN 〈 6, all but one of the top ten differentially expressed genes showed decreased expression in the latter group; i.e . when the RNA became degraded. Ontological mapping using GoMiner (p ≤ 0.05; ≥ 3 genes changed) revealed deoxyribonuclease activity, collagen, regulation of cell adhesion, cytosolic ribosome, and NADH dehydrogenase activity, to be the five categories most affected by RNA quality. Conclusion The results indicate that the Manual and RIN methods are superior to the Ratio method for evaluating RNA quality in fresh frozen breast cancer tissues. The objective measurement when using the RIN method is an advantage. Furthermore, the inclusion of samples with degraded RNA may profoundly affect gene expression levels.
    Type of Medium: Online Resource
    ISSN: 1471-2199
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2007
    detail.hit.zdb_id: 2041506-0
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  International Journal of Gynecological Pathology Vol. 37, No. 2 ( 2018-03), p. 101-109
    In: International Journal of Gynecological Pathology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 2 ( 2018-03), p. 101-109
    Abstract: The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ 2 test. A dataset of 〉 1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51%) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1–2.5), P =0.020 and HR=1.6 (1.0–2.4), P =0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0–2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker ( P =0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1–1.5), P 〈 0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7–2.0), P =0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear.
    Type of Medium: Online Resource
    ISSN: 0277-1691
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2071024-0
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