ABSTRACT: Genome-wide DNA-methylation profiling of intra- and extracranial melanoma metastases. The goal of the study was to identify differences between methylomes of intra- and extracranial metastases. For each metastasis, FFPE material was used to extract genomic DNA from a punch biopsy of a marked metastasis area. The Illumina Infinium MethylationEPIC array was used for hybridization.
Project description:An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and protein expression and activation, quantitatively analyzed by mass-array genotyping, molecular inversion probe arrays, microarrays and reverse phase protein array (RPPA) were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors. Somatic copy number variation (CNV) in 47 melanoma brain metastases (BM, except for patient 01, who had a spinal cord metastasis) and extracranial metastases (EM) were analyzed by molecular inversion probe (MIP) array (Affymetrix OncoScan FFPE Express 2.0). DNA were extracted from regions with >70% viable tumor cells from formalin-fixed and paraffin-embedded (FFPE) tissues. Of the 47 tumor samples, 22 were matched BM and EM from the same patients. In addition, 24 DNA samples from normal tissues were included as diploid controls.
Project description:An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and protein expression and activation, quantitatively analyzed by molecular inversion probe arrays, microarrays and reverse phase protein array (RPPA) were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors. Seventy-two samples from 52 brain (except for patient 01, who had a spinal cord metastasis) and extracranial metastases of melanoma were analyzed. Available biological replicates (different parts of the same tumor) were included.
Project description:An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and protein expression and activation, quantitatively analyzed by molecular inversion probe arrays, microarrays and reverse phase protein array (RPPA) were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors.
Project description:HER3 (ErbB3) belongs to a family of receptor tyrosine kinases together with the known oncogenes EGFR and HER2. Recently, antibody drug conjugates (ADCs) targeting these receptors showed promising clinical activity in extracranial malignancies of breast and lung cancer. We aimed to investigate HER3 expression in breast and lung cancer brain metastases (BM) as the basis for future clinical trial design. Illumina MethylationEPIC 850k microarrays were used to analyze genome-wide DNA methylation patterns of HER3-positive (n=43) and HER3-negative (n=28) BM.
Project description:All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2).
Project description:All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2).
Project description:An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and protein expression and activation, quantitatively analyzed by mass-array genotyping, molecular inversion probe arrays, microarrays and reverse phase protein array (RPPA) were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors.
Project description:The development of metastases is a complex multi-step process manifested by diverse patterns, involving single or multiple organs and different time-courses of distant recurrences. The aim of this study was to characterise molecular patterns associated with patterns of organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases. This study includes patients with four patterns of first metastatic sites: bone only (with no visceral metastases within 6 months of first metastasis); to viscera only (with no bone metastasis within 6 months of first metastasis); to bone and visceral organs within a 6 month period; and no recorded distant metastasis. The study population was composed of 5,061 patients diagnosed with invasive primary breast cancer without distant metastasis at the time of diagnosis between 1975 and 2005 from Guyâs Hospital. From the study population, an incidence-based case-control design was used to include patients from each of the metastatic groups and a control series randomly matched to cases according to having no reported metastasis up to the calendar date of metastasis. The aim of this expression profiling study was to characterise any molecular patterns that may be associated with the organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases.
Project description:This study investigated how the depletion of natural killer (NK) cells in mice treated with a combined PD-1/CTLA-4 blockade affects the molecular profiles of intracranial tumors in a two-site B16-OVA melanoma brain metastases model. This model contains concomitant intracranial and extracranial tumors, to mimic the presence of extracranial metastases in melanoma patients with brain metastases, and intracranial responses to the combined PD-1/CTLA-4 blockade that are observed in the clinic can be reproduced in this model.
Project description:We performed a quantitative proteome comparison on formalin-fixed paraffin embedded (FFPE) tissue of metastasized and non-metastasized primary prostate cancer (PCa) and on recurrent lymph node metastases. Comparing these three sample groups, we aimed to identify proteins, that might potentially promote/supress tumor progression or metastasis formation. Proteins were quantified label-free. Proteins with interesting biological functions were followed-up by immunohistochemistry.