3331 results for "ovarian cancer"

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• Targeted Sequencing of Primary ER-positive Breast Tumors Treated with 5 Years of Tamoxifen

  Targeted massively parallel sequencing analysis was conducted on DNA extracted from archived 22-28 year old, formalin-fixed primary breast tumors from 625 patents from British Columbia treated with five years of adjuvant tamoxifen monotherapy and followed for over 10 years. Genes were selected for targeted sequencing by review of existing large-scale breast cancer sequencing studies and breast cancer literature. In total, 83 genes were identified and 3,029 probes were designed to tile across all known exons. Illumina sequencing libraries were constructed, indexed, pooled, and enriched for target sequences by hybrid-capture followed by sequencing of paired-end 100bp reads. All samples met minimum quality controls of 80% targeted space covered at 20X or greater. On average, each sample had 336M aligned bases and a mean coverage of 135.8X.

  Study phs001234

• Genetic Epidemiology of Chronic Lymphocytic Leukemia

  Chronic lymphocytic leukemia (CLL) is a subtype of B-cell lymphoproliferative disorders (LPD), and is the most common form of adult leukemia in Caucasians in the United States. Small lymphocytic lymphoma (SLL) is also a B-cell LPD and is typically considered to be the same disease as CLL, based on pathology. We consider CLL and SLL as the same disease entity, and hereafter refer to both simply as "CLL". Using genealogical databases and cancer records, the familial clustering for CLL is one of the strongest for all cancer sites, strongly implicating germline genetic risk. We ascertained CLL cases and controls for a genomewide association study (GWAS) that was undertaken as part of the International Lymphoma Epidemiology (InterLymph) consortium GWAS. Some CLL cases are also part of extended high-risk CLLpedigrees.

  Study phs001568

• Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer

  Gastric cancers are cancers of the stomach. Hereditary cancers are passed from parent to child. Researchers want to gather data about hereditary gastric cancers. Bulk RNA sequencing (RNA-seq) of signet ring cells (SRCs) and adjacent non-SRC epithelium (NEP) was performed on laser-capture microdissected (LCM) regions of interest found in risk-reducing total gastrectomy specimens from hereditary diffuse gastric cancer (HDGC) patients (Clinicaltrials.gov ID: NCT03030404). Twenty patients (6 male, 14 female) with confirmed HDGC were identified. Analysis of differentially expressed genes (DEGs) demonstrated upregulation of certain individual epithelial–mesenchymal transition (EMT) and proliferation genes. SRC regions had significant enrichment in pathways involved in T cell signaling. CIBERSORTx predicted significant increases in the presence of regulatory T cells (Tregs) specific to SRC regions.

  Study phs003422

• The function of circular RMST in neuroendocrine tumours

  Circular RNA (circRNA) is a class of noncoding RNA with regulatory potentials. Its role in the transdifferentiation of prostate and lung adenocarcinoma into neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC) remains unexplored. Here we identified circRMST as an exceptionally abundant circRNA predominantly expressed in NEPC using total RNA-seq profiling of patient samples. In addition, circRMST is also abundantly expressed in SCLC. Functional studies using shRNA, siRNA, CRISPR-Cas13 and Cas9 consistently demonstrate that circRMST is essential for tumour growth and the expression of ASCL1, a master regulator of neuroendocrine fate. Mechanistically, circRMST physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of circRMST induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of ASCL1 transcription.

  Study EGAS50000000897

• Tumor-associated preferred end coordinates and somatic variants as signatures of circulating tumor DNA

  Cell-free DNA fragmentation is a nonrandom process. We showed that cell-free DNA fragments with ends at certain genomic coordinates had higher likelihoods of being derived from hepatocellular carcinoma. Other coordinates were associated with cell-free DNA molecules originating from the liver. Quantitative assessment of cell-free DNA molecules bearing these respective groups of end signatures correlated with the amounts of tumor-derived or liver-derived DNA in plasma. There were millions of tumor-associated plasma DNA end coordinates across the genome. Due to their high prevalence, they were more readily detectable than somatic mutations as a cancer signature in plasma. Hence, detection of tumor-associated plasma DNA ends may offer a cost-effective means of capturing evidence for the presence of cancer through liquid biopsy assessment.

  Study EGAS00001003160

• Germline variant analysis in childhood AML

  Analysis of rare germline variants in childhood AML in a large panel of cancer predisposition genes (n=216) compiled from literature review, and including genes involved in familial hematological malignancies (HM) and bone marrow failure (BMF) syndromes. The prevalence of extremely rare variants in the combined childhood AML cohort (n=72) was compared to that in the Medical Genome Reference Bank (MGRB; n=2570) comprising individuals aged at least 70 years with no history of cardiovascular disease, dementia or cancer. This showed a significant increase of rare alleles in childhood AML for 100% of subset comparisons. Next additional stringent filtering was applied to determine predicted damaging germline predisposition variants. Overall, 21% of the Australian cohort and 25% of the TARGET cohort presented germline variants predicted to be damaging predisposition variants.

  Study EGAS00001006276

• Neoadjuvant Trastuzumab Response in Breast Cancer

  HER2 (ERBB2) gene amplification and overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents such as trastuzumab are effective treatments, therapeutic resistance remains a concern in HER2-positive breast cancer with 40-50% of patients having residual disease after neoadjuvant treatment with chemotherapy and trastuzumab. To investigate features that may make it possible to predict at diagnosis which cancers will be responsive to trastuzumab and chemotherapy, 48 tumor/normal DNA pairs extracted from pretreatment tumor biopsies and blood of HER2-positive breast cancer cases treated with neoadjuvant chemotherapy and trastuzumab were sequenced. Whole genome and exome sequence from tumor (average depth 49x and 71x) and normal (average depth 33x and 69x) DNA are included here as well as RNAseq data for 42 of the tumors. The study cohort was equally divided between patients who experienced pathological complete response and those with residual disease. Samples were obtained from the American College of Surgeons Oncology Group Z1041 trial (NCT00513292) and a local single-institution study (NCT00353483).

  Study phs001291

• Analysis of Epigenomes and Genome Topology in Colorectal Cancer

  When diagnosing cancer, pathologists use nuclear morphology as a hallmark of tumor cells, but the topological changes linked to alterations in the shape of the nucleus were poorly understood. To uncover the molecular changes that occur in the 3D structure of cancer genomes, we integrated topological maps for colon tumors and normal colon tissues with epigenetic, transcriptional, and imaging data. We characterized tumor-associated changes in chromatin loops, topologically associated domains (TADs), and large-scale compartments. We found that chromatin loop rewiring contributes to oncogenic gene expression programs. Whereas TAD structures are largely stable, the spatial partitioning of the open and closed genome compartments is compromised in tumors and is accompanied by hypomethylation and histone mark rearrangements. We also identified a compartment that is reorganized in tumors and is at the interface between the canonical A and B compartments. Similar changes were evident in non-malignant cells that had accumulated excessive cellular divisions. Our analyses suggest that these compartment changes repress stemness and invasion programs while inducing immunity genes, and they may therefore restrain malignant progression.

  Study phs002288

• CALGB 40601: Randomized Phase III Trial of Paclitaxel Combined With Trastuzumab, Lapatinib, or Both As Neoadjuvant Treatment of HER2-Positive Primary Breast Cancer

  This randomized phase III trial studies paclitaxel and trastuzumab with or without lapatinib to see how well they work in treating patients with stage II or stage III breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel with trastuzumab and/or lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which regimen is more effective in treating patients with breast cancer.

  Study phs001570

• Single Cell RNA-Sequencing of BCG Naive and Recurrent Non-Muscle Invasive Bladder Cancer Reveals a CD6/ALCAM-Mediated Immune-Suppressive Pathway

  Non-muscle invasive bladder cancer (NMIBC) represents 70–80% patients with newly diagnosed bladder cancer, and Bacillus Calmette-Guerin (BCG) remains a cornerstone treatment for intermediate- and high-risk NMIBC to prevent disease recurrence and progression. However, a significant number of patients experience recurrence after their first course of BCG, posing significant challenges in the management of the disease. We conducted single cell RNA sequencing (scRNA-Seq) on freshly collected NMIBC samples, distinguishing between those naive to BCG treatment and those that recurred post-BCG treatment. We observed a clear activation of inflammatory pathways across cell types during recurrence, but these were not associated with canonical immune checkpoint or T cell exhaustion phenotypes. Analysis of cell-to-cell communication revealed enhanced interactions between T cells and urothelial cells in BCG-recurrence, predominantly modulated by CD6 and activated leukocyte cell adhesion molecule (ALCAM). Furthermore, we found CD6hi T cells to be immunosuppressed and enriched in recurrent samples, suggesting a potential role for CD6 as an immune evasion signal in NMIBC.

  Study phs003742