National Cancer Institute Cancer Genome Characterization Initiative (CGCI)

ABSTRACT:

The Office of Cancer Genomics at the National Cancer Institute is sponsoring a series of studies as part of the Cancer Genome Characterization Initiative (CGCI) to assess novel emerging sequencing technologies in cancer. The CGCI program includes comprehensive characterization of the genetic aberrations found in different pediatric and/or adult tumors.

CGCI is currently characterizing Non-Hodgkin lymphomas (including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL)) and medulloblastoma (MB), with additional cancers to be characterized in the future. All data from these projects will be released into publicly accessible databases, with a majority of data in an open-access tier. A subset of data will be available only through a controlled-access tier due to patient privacy concerns.

Project Descriptions by Disease are as follows:

• Non-Hodgkin Lymphoma (NHL) - In combination, the lymphoid cancers (non-Hodgkin lymphoma, Hodgkin lymphoma, myeloma and chronic lymphocytic leukemia), constitute the fourth most common malignancy in both men and women in North America. Lymphomas typically have characteristic abnormal chromosomes, including translocations, indicating the relevance of mutations to how NHLs develop and behave. This project uses detailed analysis on a specific well-characterized set of tumors to provide a candidate list of genomic changes specific to and common across lymphoma types. The resulting data set will facilitate studies of clinical behavior, response to treatment, patient outcome and survival, and target pathways for therapeutic agents.
  
  CGCI investigators are probing genomic alterations more deeply than has been previously possible by using state-of-the-art RNA sequencing (mRNA-seq) and whole genome shotgun sequencing (WGS) coupled with leading edge bioinformatics, data management and analysis approaches. Specifically, 2nd-generation sequencing technologies are used to survey NHL for somatic mutations, chromosomal alterations and expression levels. Fresh-frozen biopsy material and constitutional DNA is assembled from uniformly staged, treated and followed NHL patients in British Columbia, Canada. To date the project has sequenced tumor DNA and/or RNA from 117 NHL tumor samples and 10 cell lines. This includes the genomes or exomes of 1 Follicular Lymphoma (FL) and 13 diffuse large B-cell lymphoma (DLBCL) cases, all with matched constitutional DNA sequenced to comparable depths, RNA-sequencing (mRNA-seq) of 92 DLBCL, 12 FL and 8 B-cell NHL cases with other histologies and 10 DLBCL-derived cell lines. The DLBCL cases and cell-lines are from the two major subtypes of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC).


• Medulloblastoma (MB) - Medulloblastoma is the most common malignant brain tumor found in children. In order to identify the genetic alterations in MB, copy number alterations were sought using high-density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing in a set of 22 pediatric MB samples and one matched normal blood sample. All tumor samples were obtained at the time of original surgery (pre-treatment) except for one sample, which was obtained at the time of MB recurrence.
  
  Protein-encoding transcripts to be targeted for sequencing were derived from transcripts present in the Ensembl (file date 8/27/2008), RefSeq (file date 1/18/2009), and CCDS (file date 2/02/2009) databases and downloaded from the UCSC Genome Bioinformatics site. The protein encoding transcripts were supplemented with microRNA transcripts downloaded from the Sanger miRBase Sequence Database (Release 13.0) in order to yield a combined set of transcripts representing 24,893 genes (24,178 protein encoding and 715 microRNA). The regions of interest (ROIs) targeted for sequencing comprised the entire transcribed portion of the microRNA exons and the protein encoding portion plus 4 bases of flanking sequence for the protein encoding exons. Illumina Infinium II Whole Genome Genotyping Assay employing the BeadChip platform was used to analyze the same set of tumor samples at 1,199,187 (1M-Duo) SNP loci in order to detect copy number alterations in the same set of tumors.

The projects currently involved in CGCI will provide various data to include whole genomic, transcriptomic and mutational analyses of the tumor types being studied. This page will be amended as additional projects and characterization platforms are added to the CGCI portfolio.

PROVIDER: phs000235.v3.p1 | EGA |

REPOSITORIES: EGA