A5104293094- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Breast Cancer Treatment Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Colorectal Cancer Treatments and Studies
- Genomic variations and chromosomal abnormalities
- Ferroptosis and cancer prognosis
- Gastrointestinal Tumor Research and Treatment
- Gastric Cancer Management and Outcomes
- Cancer-related Molecular Pathways
- Molecular Biology Techniques and Applications
- Breast Lesions and Carcinomas
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- Cancer Immunotherapy and Biomarkers
- Gastrointestinal disorders and treatments
- Multiple and Secondary Primary Cancers
- Advanced Breast Cancer Therapies
- Cancer Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Machine Learning in Bioinformatics
- Cancer, Lipids, and Metabolism
- HER2/EGFR in Cancer Research
- Colorectal Cancer Surgical Treatments
- Nutrition, Genetics, and Disease
Agendia (Netherlands)
2020-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2010-2017
KU Leuven
2017
Vrije Universiteit Amsterdam
2011
Stockholm University
2006
Abstract Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of samples a homogeneous well-annotated series metastatic CRC (mCRC) two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations 349 are determined. Within three treatment arms, 194 chromosomal subregions progression-free survival (PFS; uncorrected single-test P -values <0.005). These filtered for effect on messenger...
The spatial arrangement of chromatin is linked to the regulation nuclear processes. One striking aspect organization segregation heterochromatic and euchromatic domains. mechanisms this are still poorly understood. In work, we investigated link between primary genomic sequence We analyzed intranuclear a human artificial chromosome (HAC) in xenospecific mouse background comparison an orthologous region native chromosome. two regions include segments that can be assigned three major classes...
Abstract Chromosomal instable colorectal cancer is marked by specific large chromosomal copy number aberrations. Recently, focal aberrations of 3 Mb or smaller have been identified as a common phenomenon in cancer. Inherent to their limited size, these harbour one few genes. The aim this study was identify recurrent and candidate driver genes well‐defined series stage II colon cancers assess potential clinical relevance. High‐resolution DNA profiles were obtained from 38 formalin‐fixed,...
Abstract Formalin‐fixed, paraffin‐embedded (FFPE) archival tissue is an important source of DNA material. The most commonly used technique to identify copy number aberrations from chromosomal in tumorigenesis array comparative genomic hybridization (aCGH). Although analysis using FFPE challenging, several research groups have reported high quality and reproducible results aCGH. Aim this study compare the commercially available aCGH platforms suitable for high‐resolution FFPE‐derived DNA. Two...
Around 30% of all stage II colon cancer patients will relapse and die their disease. At present no objective parameters to identify high-risk patients, who benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition is inaccurate. Therefore more robust markers for prediction are needed. DNA copy number aberrations proven be prognostic markers, but not yet investigated this specific group patients. The aim the study was chromosomal that...
Around 30% of all stage II colon cancer patients will relapse and die their disease. At present no objective parameters to identify high-risk patients, who benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition is inaccurate. Therefore more robust markers for prediction are needed. DNA copy number aberrations proven be prognostic markers, but not yet investigated this specific group patients. The aim the study was chromosomal that...
Cancer is caused by somatic DNA alterations such as gene point mutations, copy number aberrations (CNA) and structural variants (SVs). Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact on carcinogenesis patient outcome remains poorly understood. This study aimed to perform a systematic analysis genes that affected CNA-associated chromosomal breaks colorectal cancer (CRC) determine relevance recurrent...
MammaPrint® (MP) is a 70-gene signature that stratifies early-stage breast cancer patients into low- and high risk of distant relapse. Further stratification MP results identifies four subgroups, ultra-low (UL), low, 1, 2, with specific prognostic predictive outcomes. BluePrint® (BP) an 80-gene classifies tumors as basal, luminal, or HER2 molecular subtype. To gain insight their biological significance, we annotated the 70- BP 80-genes respect to 10 hallmarks (HoC). Furthermore, related gene...
The metastatic process is complex and remains a major obstacle in the management of colorectal cancer. To gain better insight into pathology metastasis, we investigated genomic aberrations large cohort matched cancer primaries distant metastases from various sites by high resolution array comparative hybridization. In total, 62 primary cancers, 68 (22 liver, 11 lung, 12 ovary, omentum, lymph nodes) were analyzed. Public datasets used for validation purposes. Metastases resemble their tumors...
BluePrint (BP) is an 80-gene molecular subtyping test that classifies early-stage breast cancer (EBC) into Basal, Luminal, and HER2 subtypes. In most cases, tumors have one dominant subtype, representative of a single activated pathway. However, some show statistically equal representation more than referred to as dual subtype. This study aims identify examine subtype by BP understand their biology possible implications for treatment guidance.The scores over 15,000 tumor samples from EBC...
<h3>Objective</h3> Metastatic colorectal cancer (CRC) cells have a selective preference for certain target organs that cannot be explained by circulatory patterns alone. This study aimed to identify clinicopathological features and chromosomal aberrations of primary tumours associated with organ-specific CRC metastasis. <h3>Design</h3> Clinicopathological were investigated in patients who had exclusively hepatic (n=182) versus extrahepatic (n=139) metastases. A total 139 (n=85) metastases...
Background : Around 30% of all stage II colon cancer patients will relapse and die their disease. At present no objective parameters to identify high-risk patients, who benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition is inaccurate. Therefore more robust markers for prediction are needed. DNA copy number aberrations proven be prognostic markers, but not yet investigated this specific group patients. The aim the study was...
506 Background: The 70-gene signature, MammaPrint (MP), classifies patients (pts) with early-stage breast cancer (EBC) as having an UltraLow, Low, High 1 (H1), or 2 (H2) risk of distant recurrence. I-SPY showed that pts MP H2, HR+HER2- tumors have significantly higher response rates to neoadjuvant chemotherapy + immunotherapy relative H1 tumors. Expression-based immune deconvolution provides more detailed information about cell function beyond conventional methods enumerating tumor...
// Linda J.W. Bosch 1, 2 , Geert Trooskens 3, * Petur Snaebjornsson 2, Veerle M.H. Coupé 4 Sandra Mongera 1 Josien C. Haan Susan D. Richman 5 Miriam Koopman 6 Jolien Tol 7 Tim de Meyer 3 Joost Louwagie 8 Luc Dehaspe 8, 9 Nicole C.T. van Grieken Bauke Ylstra Henk M.W. Verheul 10 Manon Engeland 11 Iris Nagtegaal 12 James G. Herman 13 Philip Quirke Matthew T. Seymour 14 Cornelis J.A. Punt 15 Wim Criekinge Beatriz Carvalho and Gerrit A. Meijer Department of Pathology, VU University Medical...
Abstract Background Methods for predicting protein function directly from amino acid sequences are useful tools in the study of uncharacterised families and comparative genomics. Until now, this problem has been approached using machine learning techniques that attempt to predict membership, or otherwise, predefined functional categories subcellular locations. A potential drawback approach is human-designated classes may not accurately reflect underlying biology, consequently important...
Abstract Background: Invasive lobular carcinoma (ILC), the second most common histologic subtype of breast cancer, is increasingly recognized as a distinct tumor type compared to more invasive ductal (IDC). While ILC known have lower rates pathologic complete response neoadjuvant chemotherapy, tumors are biologically heterogenous. As such, genomic signatures might identify patients with who benefit from tailored treatment options. The gene expression signature MammaPrint (MP) classifies...
Abstract INTRODUCTION: Black women are 41% more likely to die from breast cancer compared White yet remain underrepresented in clinical trials and population studies. We have previously shown a higher proportion of with HR+HER2- tumors further classify as Basal-Type women, using BluePrint molecular subtyping. Other studies demonstrated 3-year recurrence rates patients Luminal-Type. To determine whether the increased frequency HR+/Basal-Type impacts long-term outcomes this cohort, we risk...
Abstract Background: Antibody-drug conjugates (ADCs) continue to emerge for the treatment of a new subset patients with HER2-low breast cancer. There is limited evidence demonstrate tumors as distinct biological subtype and why/if these benefit from ADCs. To improve our understanding this newly defined HER2 category cancers, we evaluated clinical characteristics, MammaPrint (MP), BluePrint (BP), whole transcriptomic profile cancers in FLEX study. Methods: (NCT03053193) prospective,...
Abstract Background Heterogeneity in the biology of colorectal cancer (CRC) is associated with variable responses to standard chemotherapy. We aimed identify DNA hypermethylated genes as predictive biomarkers for irinotecan treatment patients metastatic CRC. Material and Methods The presence methylation a selected panel 22 was assessed by specific PCR (MSP) on primary tumors 185 CRC treated first-line capecitabine (CAP, n=90) or combination (CAPIRI, n=95) phase III CAIRO trial. Methylation...
563 Background: The 80-gene signature (BluePrint/BP) classifies early-stage breast cancers based on functional molecular pathways as luminal, HER2, or Basal-type. In the NBRST study, 13% of immunochemistry (IHC) defined ER+ HER2- reclassified Basal-type by BP assay (ER+ Basal), and these had worse prognosis but responded better to neoadjuvant chemotherapy than classified genomically luminal-type. 70-gene risk recurrence (MammaPrint/MP) further stratifies luminal-type into low luminal A high...
517 Background: Breast cancer is the leading cause of cancer-associated death among Black women, and they are 41% more likely to die from breast compared White women. Few studies have evaluated if tumor biology differences contribute this disparity in outcomes. Similar triple negative (TNBC), hormone receptor-positive (HR+) tumors classified as Basal-Type with BluePrint genomic analysis (HR+/Basal) aggressive, higher grade, over-represented young women worse clinical TNBC associated low...