7790 results for "canc*"

in 8.48 milliseconds.

• Clonal Evolution and Heterogeneity of Osimertinib Acquired Resistance Mechanisms in EGFR Mutant Lung Cancer

  Current understanding of acquired resistance to osimertinib in EGFR-mutant lung cancer is largely based on the use of targeted sequencing platforms and cell-free DNA. In this study we examined the clonal evolution and heterogeneity of acquired resistance mechanisms to osimertinib through whole exome and RNA-sequencing of prospectively collected pre-and post-osimertinib resistant tumors and metastases at rapid autopsy. We enrolled 34 patients with histologically confirmed EGFR mutant advanced lung adenocarcinoma in a prospective Phase II clinical trial to evaluate osimertinib treatment and the use of local ablative therapy (LAT) for oligoprogressive disease (NCT02759835) in EGFR mutant NSCLC from April 2016 until data cutoff in September 2019. Patients were not selected based on oligometastatic status, rather 32/34 patients had multiple organ involvement, including lung, liver, adrenal, brain and bone. Biopsies or surgeries were performed pre-osimertinib treatment and at first progression on osimertinib. A subset of patients also underwent biopsies at second progression on osimertinib, and following end of life in-patient hospice and rapid autopsy upon death. 63% (n=15/24) of first-line osimertinib and 50% (n=5/10) of second-line osimertinib treated patients had RECIST defined partial response. Overall, 21 patients had RECIST defined first progression on osimertinib. Two patients on this trial discontinued treatment and were lost to follow up. Of the 21 patients who had RECIST defined progression, 14 patients underwent LAT (8 first-line and 6 second-line). Twelve patients had paired pre- and post-osimertinib resistant tumors and three had post-osimertinib resistant tumors available for analysis. Four patients (LAT002, LAT006, LAT014 and LAT021) consented for a rapid autopsy protocol and underwent rapid autopsy after deatH. To elucidate acquired osimertinib resistance mechanisms, we performed whole-exome (WES), targeted sequencing and RNA-seq on 66 tumors and matched germline DNA from tumor tissue obtained from a total of 15 patients.

  Study phs002001

• The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

  This study was the first-known large-scale effort to uncover the mutational spectrum of head and neck cancers. We analyzed whole-exome sequence from 92 tumor-normal pairs and retained 74 of them for significance analysis. The majority exhibited a mutational profile consistent with tobacco exposure; human papilloma virus sequence was detectable in 15% of cases. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), the analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbor mutations in genes (such as NOTCH1, IRF6, TP63) that regulate squamous differentiation, implicating alterations in this process as a major driver of HNSCC carcinogenesis. Altogether, the results suggest that large-scale exome sequencing may illuminate fundamental tumorigenic mechanisms with important therapeutic implications.

  Study phs000370

• Integrative Analysis of Lung Adenocarcinoma in Never Smokers

  We performed whole genome sequencing of lung cancers from never smoker subjects from Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval (IUCPQ-UL) (N=125), Université Côte d'Azur (Nice) (N=47), the Environment And Genetics in Lung cancer Etiology (EAGLE) study (N=27), Yale University (N=22), and Moffitt Cancer Cente (N=11).

  Study phs001697

• Childhood Cancer Data Initiative (CCDI): OncoKids - NGS Panel for Pediatric Malignancies

  This study aimed to systematically collect clinical, registry and genomic data on pediatric cancer patients, and to contribute to the CCDI Pediatric Data Ecosystem. Clinical, treatment and outcome data on 1,039 pediatric cancer patients whose molecular profile was characterized on OncoKids gene panel at Children's Hospital Los Angeles was abstracted and harmonized for submission to the NCI’s Cancer Data Service. The OncoKids panel was designed to detect DNA mutations and amplification in almost 200 oncogenes and tumor suppressor genes, a limited number of pharmacogenomic targets and 1,700 disease-associated gene fusions at the RNA level. The panel encompasses the vast majority of FDA’s relevant pediatric molecular target list, as well as additional genes associated with ultra-rare pediatric tumors. The final data elements included DNA/RNA sequence data, OncoKids test results, clinical data on demographics, diagnosis, comorbidity and adverse events and treatment data.

  Study phs002518

• Cohort-Based Genome-Wide Association Study of Glioma (GliomaScan)

  We conducted a new independent GWAS of adult glioma using 1,856 cases and 4,955 controls from 14 cohort studies belonging to the Cohort Consortium, 3 case-control studies, and 1 population-based case only study. Cases were newly diagnosed glioma [ICDO-3 codes 9380-9480 or equivalent], and controls were cancer-free at the time of glioma diagnosis. We found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to higher grade tumors being captured in the cohort studies. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

  Study phs000652

• African American Breast Cancer GWAS

  The GWAS includes African American participants from 9 epidemiological studies of breast cancer, comprising a total of 3,153 cases and 2,831 controls (cases/controls: The Multiethnic Cohort Study (MEC), 734/1,003; The Los Angeles component of The Women's Contraceptive and Reproductive Experiences (CARE) Study, 380/224; The Women's Circle of Health Study (WCHS), 272/240; The San Francisco Bay Area Breast Cancer Study (SFBCS), 172/231; The Northern California Breast Cancer Family Registry (NC-BCFR), 440/53;The Carolina Breast Cancer Study (CBCS), 656/608; The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort, 64/133; The Nashville Breast Health Study (NBHS), 310/186; and, The Wake Forest University Breast Cancer Study (WFBC), 125/153). Quality control of the GWAS data and additional details can be found in Chen et al. Hum Genet. 2013 (PMID: 22923054)

  Study phs000851

• Epigenetic Mechanisms of Inflammation and Fatigue in Head and Neck Cancer

  This was a longitudinal observational study to examine the association between fatigue and DNA methylation as well as gene expression among patients with head and neck cancer. Demographic and clinical variables were collected before chemoradiotherapy and/or at follow-up visits as appropriate. Fatigue was assessed and biosamples (for DNA methylation and gene expression) were collected before, immediately after, and at six- and twelve-months post-chemoradiotherapy.

  Study phs002106

• Sequencing to Guide Cancer Care (CanSeq)

  The overall goal of the CanSeq U01 project is to study the impact of whole-exome sequencing (WES) on the clinical care of cancer patients and oncology provider practices. The aims of Project 1 are to implement and establish the feasibility of germline and somatic WES in patients with advanced solid tumors (lung and colon); to develop a framework for interpreting and reporting for exome sequencing data; to determine the proportion of patients with "actionable items" compared to existing technologies; and to report on the percentage of patients in whom unique WES findings led to a clinical action. The aims of Project 2 are to implement a production-scale platform for WES from archival (FFPE) material; to identify biologically relevant somatic and germline alterations existing in tumor/normal DNA from individual patients; to produce an evidence-based list of clinically "actionable" genetic alterations; and to develop inferential models that predict the utility of tumor genomic data within the larger clinical context. The goals of Project 3 are to describe the impact of information derived through WES on cancer patients; to test the hypothesis that patients will want to receive information about all potentially informative somatic and germline variants; to study patients' understanding of disclosed genomic information; and to describe the experiences of oncology providers as they implement WES into cancer care delivery.

  Study phs001075

• Dana-Farber Cancer Institute (DFCI) Wu Lab/Avicenne CLL RNA-Seq Study

  Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by accumulation of CD5+ B cells in peripheral lymphoid organs, bone marrow and blood. Recently, the advent of large-scale whole-exome sequencing of hundreds of CLL samples has led to gain a comprehensive understanding of the mutational landscape of this clonal B cell malignancy, but the functional effects of the putative driver mutations thus discovered are largely unknown. In this study, we analyze RNA-seq data from CLL patients to characterize dysregulated biological pathways regarding the presence of recurrent mutations. Source of tumor is patients' PBMC isolated from peripheral blood using the Ficoll method. Purity was confirmed using flow cytometry flow (>80% in all cases).

  Study phs002335

• Genomic Sequencing of Cervical Cancers

  Cervical cancer is responsible for 10-15% of cancer related deaths in women worldwide. The etiological role of infection with high-risk human papilloma viruses (HPV) in carcinomas of the cervix is well established. In general, the development of cervical carcinomas follows a progression from persistent HPV infection through precancerous lesions to invasive cancer. Previous studies have implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as chromosome-arm level copy number alterations in the pathogenesis of cervical carcinomas. Here, we report whole exome sequencing analysis of 118 cervical carcinoma-normal paired samples from patients in Norway and Mexico, as well as transcriptome sequencing of 80 cases and whole genome sequencing of 13 tumor-normal pairs. Novel somatic mutations include recurrent E322K substitutions in the MAPK1 gene encoding the ERK2 kinase and inactivating mutations in the HLA-B gene. In addition, recurrent somatic mutations in FBXW7, EP300, and NFE2L2 are novel in the context of primary cervical carcinomas. Analysis of HPV integration sites revealed recurrent integration into the RAD51B locus as well as co-occurrence of HPV genome integration and copy number gains within several genomic loci. These findings shed new light on the pathogenesis of cervical carcinomas and suggest potential novel therapeutic targets.

  Study phs000600