The Cancer Genome Atlas - TCGA

The Cancer Genome Atlas (TCGA) is a project, begun in 2005, to catalogue genetic mutations responsible for cancer, using genome sequencing and bioinformatics. TCGA applies high-throughput genome analysis techniques to improve our ability to diagnose, treat, and prevent cancer through a better understanding of the genetic basis of this disease.

The TCGA Research Network has thus far yielded complete molecular portraits of 10 different types of cancer. Today, the TCGA and other large-scale programs are providing invaluable information that can help improve patient outcomes in a number of ways, from matching patients to existing targeted treatments, to identifying new cancer-driving genetic abnormalities that could be targeted with new drugs.

TCGA is supervised by the National Cancer Institute's Center for Cancer Genomics and the National Human Genome Research Institute funded by the US government. The Cancer Genome Atlas (TCGA) is now the biggest component of the International Cancer Genome Consortium, a collaboration of scientists from 16 nations that has discovered nearly 10 million cancer-related mutations.

Geneticists are now debating whether focus should shift from sequencing genomes to analysing function (See Reference 2)

Some Examples of The Cancer Genome Atlas in Action:

Analysis of rare endocrine cancer reveals novel genetic alterations

"In the most comprehensive molecular characterization to date of adrenocortical carcinoma, a rare cancer of the adrenal cortex, researchers extensively analyzed 91 cases for alterations in the tumor genomes. They identified several novel genetic mutations as likely mechanisms driving the disease. They also found that whole genome doubling, wherein a cell has one or more extra sets of chromosomes, as a probable driver of the disease. The study, by The Cancer Genome Atlas (TCGA) Research Network, was led by Roel Verhaak, Ph.D., MD Anderson Cancer Center, Houston, and appeared in Cancer Cell, May 9, 2016. TCGA is a collaboration jointly supported and managed by NCI and National Human Genome Research Institute. This analysis supports previous findings that overexpression of IGF2, a gene encoding a peptide hormone involved in cell growth, and mutation of TP53, a common tumor suppressor gene involved in cell cycle regulation, are hallmarks of adrenocortical carcinoma..." Read full article

TCGA study identifies genomic features of invasive lobular breast carcinoma

"Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype. The new study—a comprehensive analysis of the genomes of 817 breast tumors—builds on the research network’s 2012 analysis of IDC, and provides the first in-depth analysis of the genetic drivers of ILC. Understanding the genomic differences between the two subtypes may enable clinicians to develop more personalized approaches to treating breast cancer..." read full Article

NIH-funded study uncovers range of molecular alterations in head and neck cancers, new potential drug targets

"...Scientists found that more than 70 percent of head and neck cancers had alterations in genes for growth factor receptors (EGFR, FGFR, IGFR, MET, ERBB2, DDR2), signaling molecules (PIK3CA, HRAS) and cell division regulation (CCND1). These genes may play roles in pathways that control cell growth and proliferation, and for which therapies are either available or in development. The investigators also discovered new clues about drug resistance in head and neck cancers. They found that genes affecting about 40 percent of such cancers form key parts of a pathway that helps determine cell survival and drug resistance..." see full article

TCGA study identifies seven distinct subytypes of prostate cancer

.." These subtypes may therefore have prognostic and therapeutic implications. Of the seven subtypes, four are characterized by gene fusions (in which parts of two separate genes are linked to form a hybrid gene) involving members of the ETS family of transcription factors (ERG, ETV1, ETV4, and FLI1), and the other three are defined by mutations of the SPOP, FOXA1, and IDH1 genes. Notably, the IDH1 mutation was identified as a driver of prostate cancers that occur at younger ages. .." read full article

 

Readings and References

1-NIH - Cancer Genome Atlas

2- End of Cancer-Genome Project Prompts Rethink

3-Analysis of rare endocrine cancer reveals novel genetic alterations May 2016

4-TCGA study identifies genomic features of invasive lobular breast carcinoma

5-NIH-funded study uncovers range of molecular alterations in head and neck cancers, new potential drug targets

6-TCGA study identifies seven distinct subytypes of prostate cancer