Cancer Genome Sequencing
Cancer genome sequencing aims to assemble the "parts list" of cancer, where "parts" are genetic structures—DNA and RNA—that are altered in cancer. Genome sequencing programs that aim to characterize large collections of cancers, such as The Cancer Genome Atlas (TCGA), have already revealed a variety of oncogenic alterations. These discoveries have led to improved care for patients with many different types of cancer.
Tools and Methods
CCG characterizes tumor samples and matched normal tissue using a variety of techniques because a deep and comprehensive study of the genome can provide significantly more information about cancer biology than any single platform can. CCG’s tools include:
- Next-generation DNA exome sequencing
- Next-generation DNA whole genome sequencing
- Total RNA sequencing
- Reverse phase protein array (RPPA) protein analysis
- Epigenomic analysis
The Genome Characterization Pipeline carries out CCG’s genome sequencing research and the resulting data are made available via the Genomic Data Commons (GDC). Learn more about how CCG works and what data are produced.
Programs and Collaborations
- Changes in epidermal growth factor receptor (EGFR)
- Changes in anaplastic lymphoma receptor tyrosine kinase (ALK)
Patients with these alterations receive standard of care treatment followed by a targeted therapy that corresponds to the alteration in their tumors’ genome, erlotinib for EGFR mutations and crizotinib for ALK rearrangements. ALCHEMIST is a collaboration between CCG and NCI’s Division of Cancer Treatment and Diagnosis.
CGCI supports research to comprehensively catalog the genomic alterations in adult and pediatric cancers. The research community can use CGCI data to gain insight into the underlying mechanisms of these cancers and identify potential therapeutic targets. The HIV+ Tumor Molecular Characterization Project (HTMCP) and Burkitt Lymphoma Genome Sequencing Project (BLGSP) are two active CGCI projects. CGCI also supported the sequencing of medulloblastoma and non-Hodgkin lymphoma. View the CGCI data matrix to search and download data generated by the initiative.
Cancer of Unknown Primary (CUP) Consortium
The CUP Consortium aims to characterize the genomic landscape of 500 cases of clinically well-annotated CUPs. For 3-10% of all worldwide diagnosed cancers, the primary tissue of origin cannot be determined. Survival rates are poor for these cases of so-called Cancer of Unknown Primary, as selecting the appropriate therapy requires a basic understanding and diagnosis of a case. Epidemiological studies are also problematic as CUP cases are rare and difficult to compare, and no international standard diagnostic code exists.
By comparing the molecular profiles of CUPs with primary tumors of known origin, the consortium aims to better understand these challenging cases, develop a robust clinical tool for predicting primary sites, and elucidate the impact of specific-site tailored therapies on survival.
CTSP launched out of a joint aspiration of CCG and NCI’s Division of Cancer Treatment and Diagnosis (DCTD) to promote the use of genomics in NCI-sponsored clinical trials of the National Clinical Trials Network (NCTN). CTSP’s goal is to elucidate the molecular basis of response and resistance to therapies studied. The cancer types currently under study are breast cancer, renal cell carcinoma, and diffuse large B-cell lymphoma.
The EOMI, a collaboration between CCG and the Division of Cancer Prevention's NCI Community Oncology Research Program (NCORP), studies the molecular characteristics of six cancers that develop at an earlier age and may occur in higher rates and/or be more aggressive in some populations. By characterizing cancers from NCORP's minority/underserved community sites, the initiative is investigating how biology may underpin these disparities.
The ER Initiative aims to understand the genetic basis of some cancer patients' dramatically positive responses to particular drug therapies that are not effective for most other patients. This pilot study is characterizing the genomic profiles of 100 "exceptional responder" patients who were treated for a variety of different types of cancer. The Exceptional Responders Initiative is a joint initiative of CCG and the Division of Cancer Treatment and Diagnosis (DCTD).
NCI has dedicated resources to characterizing refractory cancers—cases that do not respond to treatment or become resistant during treatment. These cancers, such as peripheral T- and NK-cell lymphoma and glioblastoma, are associated with very poor outcomes and can vary greatly in both molecular features and clinical presentation. Many refractory cancers cannot be classified using current diagnostic methods. This program aims to gain a better understanding of refractory cancers and help meet the urgent need for new diagnostics and therapies.
TARGET applies comprehensive genomic approaches to determine molecular changes that drive certain childhood cancers, including aggressive and hard to treat subsets of acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, osteosarcoma, and several types of kidney tumors. TARGET investigators collaborate with the NCI-supported Children's Oncology Group and NCI's Cancer Therapy Evaluation Program (CTEP), which facilitates discovery of molecular targets and the rapid translation of those findings to the clinic.
TCGA is a collaboration between the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) that has generated comprehensive, multi-dimensional maps of the key genomic changes in 33 types of cancer. The TCGA dataset, comprising more than two petabytes of genomic data, is publically available and helps the cancer research community improve the prevention, diagnosis, and treatment of cancer.
In April 2018, the Cancer Genome Atlas (TCGA) Research Network marked the end of the TCGA program by publishing the Pan-Cancer Atlas, a final collection of cross-cancer analyses delving into overarching themes on cancer.