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 a number of B-cell non-Hodgkin lymphomas (including diffuse large B-cell lymphoma (DLBCL) from patients with and without HIV+ infection, follicular lymphoma (FL), as well as adult and pediatric Burkitt lymphomas), medulloblastoma (MB), additional HIV-associated tumors (including lung and cervical cancers); additional tumor types may 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.

Individual project descriptions are available by disease on the substudy pages (links are included at the top of this page). Brief summaries are as follows:

• Non-Hodgkin Lymphoma (NHL) - 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. 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) - 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. 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.


• HIV+ Tumor Molecular Characterization Project (HTMCP) - This project is a joint effort of the Office of Cancer Genomics (OCG) and the Office of HIV and AIDS Malignancy (OHAM). Its goals are to characterize HIV-associated cancers (obtained from HIV-infected patients) and compare them to the same types of cancers from patients without HIV infection. Investigators will perform 30X genome sequencing of 100 cases of paired tumor and germline DNA, along with transcriptome sequencing in each of 3 types of HIV+ tumors (DLBCL, lung and cervical cancers). These platforms allow discovery of mutations both in coding and non-coding genomic regions, gene expression and genomic alterations (including translocations, insertions and deletions). Comparing tumors of cancer patients both with and without HIV-infection will provide insight into the potential function of this virus in certain cancers.


• Burkitt Lymphoma Genome Sequencing Project (BLGSP) - This project is a collaborative effort between the National Cancer Institute and the Foundation for Burkitt Lymphoma Research to develop a databank of the many alterations found in Burkitt lymphoma (BL), an uncommon type of Non-Hodgkin lymphoma that occurs most often in children and young adults. The goal of the BLGSP is to explore potential genetic changes in patients with BL that could lead to better prevention, detection and treatment of the cancer. The project will characterize the alterations of the tumors' genomes (with matched normal as control) and transcriptomes by sequencing the DNA and RNA of each case. Using the data generated, the ultimate goals of the project are to discover the molecular changes that are present in BL patients and then determine how those changes correlate with treatment regimen and outcome.

As described above, the projects currently involved in CGCI will provide various data to include whole genomic, transcriptomic (mRNA-seq and miRNA-seq) 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.