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- Jönsson, Göran B, et al.
(författare)
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Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics
- 2010
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used to dissect this complexity and to stratify tumors into intrinsic gene-expression subtypes, associated with distinct biology, patient outcome, and genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes. Methods: We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer. Results: We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis. Conclusions: Global DNA copy-number analysis integrated with gene-expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may prove useful for understanding the mechanisms of tumor development and for prognostic and treatment prediction purposes.
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| 2. |
- Luts, Heleen, et al.
(författare)
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Multicenter evaluation of signal enhancement algorithms for hearing aids
- 2010
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 127:3, s. 1491-1505
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the European HearCom project, promising signal enhancement algorithms were developed and evaluated for future use in hearing instruments. To assess the algorithms' performance, five of the algorithms were selected and implemented on a common real-time hardware/software platform. Four test centers in Belgium, The Netherlands, Germany, and Switzerland perceptually evaluated the algorithms. Listening tests were performed with large numbers of normal-hearing and hearing-impaired subjects. Three perceptual measures were used: speech reception threshold (SRT), listening effort scaling, and preference rating. Tests were carried out in two types of rooms. Speech was presented in multitalker babble arriving from one or three loudspeakers. In a pseudo-diffuse noise scenario, only one algorithm, the spatially preprocessed speech-distortion-weighted multi-channel Wiener filtering, provided a SRT improvement relative to the unprocessed condition. Despite the general lack of improvement in SRT, some algorithms were preferred over the unprocessed condition at all tested signal-to-noise ratios (SNRs). These effects were found across different subject groups and test sites. The listening effort scores were less consistent over test sites. For the algorithms that did not affect speech intelligibility, a reduction in listening effort was observed at 0 dB SNR. (C) 2010 Acoustical Society of America. [DOI: 10.1121/1.3299168]
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| 3. |
- Staaf, Johan, et al.
(författare)
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Identification of Subtypes in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Reveals a Gene Signature Prognostic of Outcome.
- 2010
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 28:11, s. 1813-1820
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) with variable prognosis and response to therapy. We aimed to investigate the heterogeneous biologic appearance and clinical behavior of HER2-positive tumors using molecular profiling. PATIENTS AND METHODS: Hierarchical clustering of gene expression data from 58 HER2-amplified tumors of various stage, histologic grade, and estrogen receptor (ER) status was used to construct a HER2-derived prognostic predictor that was further evaluated in several large independent BC data sets. RESULTS: Unsupervised analysis identified three subtypes of HER2-positive tumors with mixed stage, histologic grade, and ER status. One subtype had a significantly worse clinical outcome. A prognostic predictor was created based on differentially expressed genes between the subtype with worse outcome and the other subtypes. The predictor was able to define patient groups with better and worse outcome in HER2-positive BC across multiple independent BC data sets and identify a sizable HER2-positive group with long disease-free survival and low mortality. Significant correlation to prognosis was also observed in basal-like, ER-negative, lymph node-positive, and high-grade tumors, irrespective of HER2 status. The predictor included genes associated with immune response, tumor invasion, and metastasis. CONCLUSION: The HER2-derived prognostic predictor provides further insight into the heterogeneous biology of HER2-positive tumors and may become useful for improved selection of patients who need additional treatment with new drugs targeting the HER2 pathway.
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| 4. |
- Van den Bosch, T., et al.
(författare)
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Detection of intracavitary uterine pathology using offline analysis of three-dimensional ultrasound volumes: interobserver agreement and diagnostic accuracy
- 2012
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:4, s. 459-463
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Tidskriftsartikel (refereegranskat)abstract
- Objective To estimate the diagnostic accuracy and interobserver agreement in predicting intracavitary uterine pathology at offline analysis of three-dimensional (3D) ultrasound volumes of the uterus. Methods 3D volumes (unenhanced ultrasound and gel infusion sonography with and without power Doppler, i.e. four volumes per patient) of 75 women presenting with abnormal uterine bleeding at a bleeding clinic were assessed offline by six examiners. The sonologists were asked to provide a tentative diagnosis. A histological diagnosis was obtained by hysteroscopy with biopsy or operative hysteroscopy. Proliferative, secretory or atrophic endometrium was classified as normal histology; endometrial polyps, intracavitary myomas, endometrial hyperplasia and endometrial cancer were classified as abnormal histology. The diagnostic accuracy of the six sonologists with regard to normal/abnormal histology and interobserver agreement were estimated. Results Intracavitary pathology was diagnosed at histology in 39% of patients. Agreement between the ultrasound diagnosis and the histological diagnosis (normal vs abnormal) ranged from 67 to 83% for the six sonologists. In 45% of cases all six examiners agreed with regard to the presence/absence of intracavitary pathology. The percentage agreement between any two examiners ranged from 65 to 91% (Cohen's ?, 0.310.81). The Schouten ? for all six examiners was 0.51 (95% CI, 0.400.62), while the highest Schouten ? for any three examiners was 0.69. Conclusion When analyzing stored 3D ultrasound volumes, agreement between sonologists with regard to classifying the endometrium/uterine cavity as normal or abnormal as well as the diagnostic accuracy varied substantially. Possible actions to improve interobserver agreement and diagnostic accuracy include optimization of image quality and the use of a consistent technique for analyzing the 3D volumes. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 5. |
- Van den Bosch, T., et al.
(författare)
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Effect of gel-instillation sonography on Doppler ultrasound findings in endometrial polyps
- 2011
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 38:3, s. 355-359
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Tidskriftsartikel (refereegranskat)abstract
- Objective Saline infusion sonohysterography has been reported to suppress the color signal within the endometrium at color or power Doppler evaluation. The aim of this study was to evaluate if gel-instillation sonography (GIS) affects the power Doppler signal in patients with endometrial polyps. Methods Ultrasound volumes of the uterus, obtained by three-dimensional ultrasound imaging of 25 women with histologically confirmed endometrial polyps, were assessed offline by six gynecologists with a special interest in gynecological ultrasound. Each woman contributed four volumes: one gray-scale volume and one power Doppler volume before GIS, and one gray-scale volume and one power Doppler volume at GIS. Power Doppler features before and after gel infusion were compared. Results At unenhanced ultrasound a pedicle artery was seen in 27-46% of cases, whereas, after gel infusion the examiners reported a pedicle artery in 30-46% of cases (Exact McNemar's test P-values ranged from 0.50 to 1.00). The level of agreement between unenhanced ultrasound and GIS ranged from 59 to 91% (Cohen's kappa values ranged from 0.17 to 0.79). There was no tendency for a pedicle artery to be identified less often at GIS than before gel instillation. Conclusion Gel infusion does not affect the power Doppler signal in patients with endometrial polyps. Copyright. (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
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