16468 results for "sec+and+unspecified+malignant+neoplasm"

in 36.13 milliseconds.

• Circulating Tumor DNA Analysis Detects Minimal Residual Disease and Predicts Recurrence in Patients with Stage II Colon Cancer

  Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify those at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively-parallel-sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected post-operatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of the 164 patients with negative ctDNA (HR, 18; 95% confidence interval [CI], 7.9 to 36; P<0.001). In patients treated with chemotherapy, the presence of ctDNA following completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P=0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

  Study EGAS00001001839

• Clonal dynamics after allogeneic haematopoietic cell transplantation using genome-wide somatic mutations - TGS

  Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those harvested from a donor, and is received by 40,000 patients worldwide each year. To quantify dynamics of long-term stem cell engraftment, we sequenced whole genomes of 2,824 single-cell-derived haematopoietic colonies from blood samples of 10 donor-recipient pairs taken 9-31 years after HLA-matched sibling HCT. With younger donors, 10,000-50,000 stem cells had engrafted and were still contributing to haematopoiesis at time of sampling, but estimates were 10-fold lower with older donors. Engrafted stem cells made multilineage contributions to myeloid, B-lymphoid and T-lymphoid populations, although individual clones often showed biases towards one or other mature cell type. Recipients had lower clonal diversity than matched donors, equivalent to ~10-15 years of additional ageing, arising from up to 25-fold greater expansion of stem cell clones. An HCT-related population bottleneck alone could not explain these differences: instead, phylogenetic trees evinced two distinct modes of HCT-specific selection. In 'pruning selection', cell divisions underpinning recipient-enriched clonal expansions had occurred in the donor, preceding transplant - their selective advantage derived from preferential mobilisation, harvest, survival ex vivo or initial homing. In 'growth selection', cell divisions underpinning clonal expansion occurred through proliferative advantage in the recipient's marrow after homing - clones with multiple driver mutations especially demonstrated this pattern. Uprooting stem cells from their native environment and transplanting them to foreign soil exaggerates selective pressures, distorting and accelerating the loss of clonal diversity compared to the unperturbed haematopoiesis of donors.

  Dataset EGAD00001010874

• Phylogenetic analysis of treatment-naive metastases using whole exome and genome sequencing data

  Metastases are responsible for the majority of cancer related deaths and are often difficult to treat successfully. Even for metastases that occur subsequent to treatment, we do not know whether such relapsing metastases were originally heterogeneous or if the observed heterogeneity is a consequence of therapy. Given that treatment can influence evolutionary dynamics by selecting resistant clones, imposing bottlenecks on cancer cell populations, and even inducing novel somatic mutations, characterizing the prior standing variation among metastases remains an important goal to predict initial therapeutic response. To quantify the heterogeneity at clinical presentation of advanced disease, we surveyed the literature for patients in which at least two treatment-naïve metastases underwent genome/exome-wide sequencing. Across all cancer types surveyed, only 18 subjects were found to fulfill this requirement. Including previously unpublished data from two subjects, we analyzed data of 74 untreated metastases and inferred cancer phylogenies. Putative driver gene mutations were acquired at a 2-fold higher rate on the trunk of all metastases than on branches. Mutations in driver genes along the trunk were strongly enriched for predicted functional consequences. Using a stochastic mathematical model, we find that driver gene heterogeneity among metastases mostly occurs in slowly growing cancers for highly advantageous driver gene mutations. Seeding efficiency only weakly affects the heterogeneity among metastases. These results explain why functional driver gene heterogeneity is uncommon in advanced disease prior to treatment, thus providing optimism for future therapies that depend on mutations across metastases.

  Study EGAS00001002777

• Clonal selection after gene therapy in sickle cell disease

  While gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD), the occurrence of myeloid malignancies in clinical trials has prompted concern. To interrogate potential mechanisms underlying increased cancer risk, we used hematopoietic stem cell (HSC) clonal tracking by whole genome sequencing (WGS) to map the somatic mutation and clonal landscape of 2,592 gene modified as well as unmodified single stem and progenitor cells from six SCD patients undergoing gene therapy (7-26 years old, average 12.7× depth). Pre-GT phylogenetic trees in SCD were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified. However, an increased frequency of driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) were seen in both genetically modified and unmodified cells suggested positive selection of mutant clones during gene therapy. This work sheds light on the mutation landscape and HSC clonal dynamics in gene therapy for SCD and highlights enhanced fitness of some HSCs harboring pre-existing driver mutations following gene therapy. Future studies should define the long-term fate of mutant clones including any contribution to expansions associated with myeloid neoplasms.

  Dataset EGAD00001010913

• MSI-Exome-DAC Team Microsatellites Instability and Cancer, INSERM Hospital Saint-Antoine, Paris 12, France Carte d'identité des tumeurs, French league against cancer, Paris France

  Dac EGAC00001000665

• UCSF Sebaceous Carcinoma DAC for review of sequence data release from manuscript in Nature Communications, based in the UCSF Departments of Dermatology and Pathology

  Dac EGAC00001000850

• Early on-treatment changes in circulating tumor DNA fraction and response to enzalutamide or abiraterone in metastatic castration-resistant prostate cancer - Data Access Committee

  Dac EGAC00001003128

• RNA Editing Transcriptome

  Transcriptome sequencing data of tumor and 10 matched normal samples of the EGAS00001000495 project

  Dataset EGAD00001000627

• RNA-seq data from diagnosis and relapse samples of Down Syndrome acute lymphoblastic leukemia.

  Dataset EGAD00001003280

• miRNA profiling of human plucked hair follicle

  miRNA profiling of human plucked hair follicle from frontal and occipital scalp

  Dataset EGAD00010001500

• leukemia_2 SNP6.0

  Over 1.87 million SNP and CNV loci are screened by Affymetrix SNP 6.0 array

  Dataset EGAD00010001814

• germline_2 SNP6.0

  Over 1.87 million SNP and CNV loci are screened by Affymetrix SNP 6.0 array

  Dataset EGAD00010001813

• BLEMD (arrays set)

  Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma (arrays set)

  Dataset EGAD00010001857

• dataset_raw_NativesAmericans_LDGH_august2020

  Genome-wide data for 98 Native American individuals from Andes and Amazon

  Dataset EGAD00010001958

• BreastCancer_Miroarrays

  Genotyping array data for breast cancer and matched normal mammary gland samples

  Dataset EGAD00010002251

• Gentoypes_Lesotho

  Individuals genotyped on the Illumina GSA v2. Autosome and X chromosome.

  Dataset EGAD00010002468

• High throughput profiling of undifferentiated pleomorphic sarcomas identifies two main subgroups with distinct immune contexture, clinical outcome and sensitivity to targeted therapies

  Study EGAS00001004612

• Mutation and Microsatellite Burden Predict Response to PD-1 Inhibition in Children with Germline DNA Replication Repair Deficiency: An Observational Registry Study

  Study EGAS00001005579

• UTSW KCP DAC

  This DAC manages access to WES and RNA-Seq data from studies approved under the IRBs of KCP principal investigators.

  Dac EGAC50000000203

• ORIENT study

  scRNAseq dataset containing 5 healthy donors and 4 asthmatic donors.

  Dataset EGAD00001009687

• RRBS melanoma biopsies

  RRBS data for melanoma biopsies at baseline and after treatment

  Dataset EGAD00001009060

• Melanoma multi site metastases

  These are caveman, pindel, battenberg and brass calls for index patients' metastatic melanoma genomes within this study.

  Dataset EGAD00001005483

• KRAS Mutations in Multiple Myeloma

  Fastq files for 80 Multiple Myeloma Patients and 12 cell-lines

  Dataset EGAD00001005743

• Disorders of growth and insulin action

  Illumina paired-end sequencing of whole- exome pulldown DNA from Severe Insulin Resistant patients.

  Dataset EGAD00001000381

• Multisample2 Amplicon

  Amplicon data of tumor samples generated for validation of WES findings and further sub clonal mapping

  Dataset EGAD00001004020