Cancer Genomics

cancergenomics

All the DNA contained in your cells makes up your genome. In most cells, the genome is packaged into two sets of chromosomes: one set from your mother and one set from your father. These chromosomes are composed of six billion individual DNA letters. Just like the letters in a book make words to tell a story, so do the letters in our genomes. Genomics is the study of the sequence of these letters in your DNA and how each string of letters passes information to help each cell in your body work properly.

In cancer cells, small changes in the genetic letters can change what a genomic word or sentence means. A changed letter can cause the cell to make a protein that doesn’t allow the cell to work as it should. These proteins can make cells grow quickly and cause damage to neighboring cells. By studying the cancer genome, scientists can discover what letter changes are causing a cell to become a cancer. The genome of a cancer cell can also be used to tell one type of cancer from another.

The study of cancer genomes has revealed abnormalities in genes that drive the development and growth of many types of cancer. This knowledge has improved our understanding of the biology of cancer and led to new methods of diagnosing and treating the disease.

Cancer Genomics Overview

Cancer is a group of diseases caused by changes in DNA that alter cell behavior, causing uncontrollable growth and malignancy. These abnormalities can take many forms, including DNA mutations, rearrangements, deletions, amplifications, and the addition or removal of chemical marks. These changes can cause cells to produce abnormal amounts of particular proteins or make misshapen proteins that do not work as they should. Oftentimes, a combination of several genomic alterations work together to promote cancer.

Genetic alterations can be inherited from one’s parents, caused by environmental factors, or occur during natural processes such as cell division. The changes that accumulate over one’s lifetime are called acquired or somatic changes, and account for 90 to 95 percent of all cases of cancer.

By sequencing the DNA and RNA of cancer cells and comparing the sequences to normal tissue such as blood, scientists identify genetic differences that may cause cancer. This approach, called structural genomics, may also measure the activity of genes encoded in our DNA in order to understand which proteins are abnormally active or silenced in cancer cells, contributing to their uncontrolled growth.

By sequencing the DNA and RNA of cancer cells and comparing the sequences to normal tissue such as blood, scientists identify genetic differences that may cause cancer. This approach, called structural genomics, may also measure the activity of genes encoded in our DNA in order to understand which proteins are abnormally active or silenced in cancer cells, contributing to their uncontrolled growth.

Importance of Cancer Genomics in Precision Cancer Medicine

Genomic information about cancer is leading to better diagnoses and treatment strategies that are tailored to patients’ tumors, an approach called precision medicine. As a result of research into the genomic changes associated with cancer, drugs have been developed to fight the disease in several ways:

  • Inhibiting enzymes that trigger the abnormal growth and survival of cancer cells
  • Blocking aberrant gene expression characteristic of cancer cells
  • Halting molecular signaling pathways that are in overdrive in cancer cells

This makes them less likely to be toxic for patients compared to other treatments such as chemotherapy and radiation that can kill normal cells. There are several examples of precision medicine already in clinical use:

  • Imatinib (Gleevec) inhibits overactivity of a protein (called Bcr-Abl tyrosine kinase) in patients whose leukemia is caused by a particular chromosomal rearrangement.
  • Trastuzumab (Herceptin) controls a hyperactive signaling pathway (HER2 tyrosine kinase) caused by multiple copies of the HER2 gene in a subtype of breast cancers.

Challenges in Cancer Genomics Research

Comprehensive analysis of cancer genomes has revealed a great deal of diversity in the genetic abnormalities found within cancers of a single type. Moreover, recurrent genetic alterations within these cancers are often involved in only a small percentage of cases. Identifying which genetic changes initiate cancer development and discovering rare genetic alterations that drive cancers are therefore challenges for the field.

Another challenge is acquiring high-quality biological samples needed for genomic studies, particularly for tumor types that are uncommon or rare, or those not treated primarily by surgery.

Developing cell lines and animal models that capture the diversity of human cancer is also an unmet need. Models of rare cancer subtypes may be nonexistent or underrepresented, and there are no models for many recurrent genetic lesions in human cancer.

Managing and analyzing the vast amounts of data involved in genomic studies are additional challenges for the field. This area of research requires an efficient bioinformatics infrastructure and increasingly involves contributions of data and expertise from cross-disciplinary teams.