Project description:Primary central nervous system lymphoma (PCNSL) is a distinct extranodal lymphoma presenting with limited stage disease but variable response rates to treatment despite homogenous pathological presentation. The likely underlying molecular heterogeneity and its clinical impact is poorly understood. The present dataset contents paired-ended whole-exome sequencing information (n=115; HyperExome Kapa hyperprep), paired-ended RNA-seq information (n=123; KAPA mRNA HyperPrep Kits), and paired-ended bisulfite sequencing (n=64; TruSeq Methyl Capture EPIC) from fresh-frozen tumor tissue immunocompetent, treatment naïve PCNSL patients. Additionally, the dataset includes single-ended RNA-seq (n=93; QuantSeq 3’ mRNA-Seq Library Prep Kit) from formalin-fixed, paraffin-embedded tissue of immunocompetent, treatment naïve PCNSL patients. All samples were sequenced in an Illumina NovaSeq 6000 instrument.
Project description:High-grade serous ovarian cancer (HGSOC) is the deadliest gynecologic malignancy in women.The lack of effective second line therapeutics remains a substantial challenge for BRCA-1/2 wildtype HGSOC patients, and contributes to poor survival rates due to drug resistance. There is a striking need to elucidate and implement new and alternative treatment options for patients with HGSOC. Histone Deacetylases (HDACs) are promising targets in HGSOC treat-ment, however, the mechanism and efficacy of HDAC inhibitors is understudied in HGSOC. In order to consider HDACs as a treatment target, we need to better understand how they are functioning within HGSOC. This includes elucidating HDAC6 protein-protein interactions. In this study, we carried out substrate trapping to elucidate HDAC6-specific interactors in the context of BRCA-1/2 wildtype HGSOC
Project description:We characterized transcriptional patterns of chemotherapy resistance in high-grade serous ovarian cancer (HGSOC) using patient-derived prospective tissue sample pairs before and after treatment at single-cell resolution. Our cohort consists of scRNA-seq data from treatment-naïve and post-neoadjuvant chemotherapy (post-NACT) pairs from 11 homogeneously treated HGSOC patients. After quality control, we obtained 51,786 cells, including 8,806 malignant epithelial (tumor), 8,045 stromal and 34,935 immune cells. Our unbiased analysis reveals how chemotherapy modulates cancer cell states by both subclonal selection and microenvironment boosted transcriptional induction across the homogeneously treated sample cohort. Our results define a cell state that allows biomarker-based prediction and targeting of chemoresistance.
Project description:The goal of this study was to compare transcription profiles of high grade serous ovarian cancer (HGSOC) patients at Day 0 and Day 15 of a single course Prexasertib treatment at 105mg/m2 intravenously over 1 hour. HGSOC patients recruited for this study were women aged 18 and older with most (79%) showing platinum resistant or refractory disease. Total RNA from patients before (Day 0, n=18) and 2 weeks after Prexasertib treatment (Day15, n=11) were prepared from frozen biopsies, and analysed using HiSeq4000 using Illumina TruSeq Stranded Total RNA Library Prep and paired-end sequencing. Data is shown as quartile normalized CPM-TMM values. Patient survival and response was monitored till end of study. Our study show that prexasertib has clinical benefit in HGSOC patients.
Project description:Our data suggest that neoadjuvant chemotherapy enhances anti-cancer responses of T cells in peritoneal metastases of patients with high-grade serous ovarian cancer but does not decrease levels of immune checkpoint molecules, providing a rationale for sequential chemo-immunotherapy. tRNA was isolated from 35 omental tissue samples of HGSOC metastases either pre or post NACT treatment. RNASeq was performed on poly-A selected mRNA fragments, 100 b.p paired end, and strand specific, on average 40 million reads per sample.
Project description:We reveal three-dimensional patterns of tumour growth by exploiting the unique metastasizing patterns of treatment naïve stage IIIC/IV epithelial ovarian cancer. We performed topographic mapping of structural genomic rearrangements, coding mutations, copy number changes and RNA expression in biopsies derived from 27 primary and metastatic sites across three patients. Based on somatic genomic changes, we performed sample clustering and obtained unique insight in natural tumour growth and spread. Based on extensive multi-level profiling, our data highlight the diverse modes of epithelial ovarian cancer development before applying selective pressure from therapy. We performed SNP array analysis on tumor biopsies from 3 patients (P1, P2, P3) with advanced stage ovarian cancer. This submission includes SNP data for 26 tumor biopsies and 5 normal tissue samples.
Project description:Limited evidence exists on the extent and impact of spatial and temporal heterogeneity of high grade serous ovarian cancer (HGSOC) on tumour evolution and patients surgical and clinical outcome. We investigated this through systematic mapping of multi-site tumours at initial presentation and matched relapse from 49 chemo-naïve HGSOC patients with high tumour load, operated upfront.
Our data provides a unique insight into the tumour evolution and metastatic pathways of HGSOC across time and space, how this
complexity relates to surgical and clinical outcome and its consequences on clinical decision-making.
Project description:This study was conducted to determine why some high grade serous ovarian cancer (HGSOC) patients recur earlier than others following treatment
Project description:Neoadjuvant treated patients were selected from the Genomstudy of the University Women`s Clinic Heidelberg (2009-2016). This study includes primary breast cancer cases that were newly diagnosed at the University women's clinic of Heidelberg and had given their informed consent for participating in this study. This study was approved by the Ethical Committee of the Medical Faculty in Heidelberg. All cases were female and Caucasian. Fresh core needle biopsies and fresh tumor tissue were examined by a pathologist, snap-frozen in liquid nitrogen and stored at -80C within 15 min after sampling. Total RNA as well as DNA and protein were extracted by applying the QIAGEN All Prep Kit. All eluates were stored at -80C until usage. A sample swap most probably occurred for patient 207, so 207-S is actually in the T condition and 207-T in the S condition.