Genetics and Hereditary Cancer

We are a mass of genes, about 25,000 different genes in each cell of our bodies. These genes control how the cell works, how quickly it grows, how often it divides and how long it lives. We have two sets of 23 chromosomes that contain these genes, one set inherited from each parent.

Cancer happens when a gene in a cell mutates, or changes. This creates an abnormal protein that provides information to the cell which causes it to grow uncontrollably and form a cancer. Gene mutations may be inherited or acquired.

Acquired gene mutations are by far the most common cause of cancer, and happen because of damage to genes during a person’s life.  Damage may occur from exposure to tobacco, ultraviolet (UV) light, radiation, chemicals, viruses or aging. Multiple mutations must occur in a cell for a cancer to develop. Acquired gene mutations are not passed on from your parents. Acquired gene mutations occur spontaneously.

Siteman Cancer Center is involved in studying the genetic make up of tumors and documenting the acquired mutations that occur in many cancer types. Detailing a specific cancer’s unique genetic signature provides vital information for matching treatments to specific  cancers. Researchers and oncologists work closely to identify treatments that match a particular tumor’s genome. In doing so, the treating physician has a better idea which treatments many be most effective for a person’s specific tumor.

Approximately 10 percent of all cancers types arise not from acquired gene mutations that develop spontaneously, but from inherited gene mutations, which are passed directly from a parent to a child. Since these types of gene mutations are present from birth, people with inherited gene changes in certain genes have a higher chance to develop different types of cancer. The types of cancer are based on the specific gene that has an inherited gene mutation. People with an inherited gene mutation leading to an increased chance to develop cancer are said to have hereditary cancer or have a hereditary cancer predisposition.

The Hereditary Cancer Program provides assessment, education and genetic testing for families to identify if they have hereditary cancer. The goal of the assessment is to identify families who have an increased cancer risk and to use this information to guide their medical care.

The McDonnell Genome Institute (MGI)

The McDonnell Genome Institute (MGI) is a world leader in the fast-paced, constantly changing field of genomics. A truly unique institution, it pushes the limits of academic research by creating, testing, and implementing new approaches to the study of biology with the goal of understanding human health and disease, as well as evolution and the biology of other organisms.

As one of only three NIH funded large-scale sequencing centers in the United States, the McDonnell Genome Institute is helping to lead the way in high-speed, comprehensive genomics. It began as a key player in the Human Genome Project – an international effort to decode all 6 billion letters of our genetic blueprint – ultimately contributing 25 percent of the finished sequence, and continuing to work in concert with a number of other genome sequencing centers around the world.

A major goal of the McDonnell Genome Institute is to advance the emerging field of cancer genomics. In 2008, the McDonnell Genome Institute became the first to sequence the complete genome of a cancer patient — a woman with leukemia — and to trace her disease to its genetic roots. They have since sequenced the genomes of many cancer patients including those with breast, lung, ovarian and brain tumors. The McDonnell Genome Institute has also initiated a major landmark project with St. Jude Children’s Research Hospital to sequence the genomes of several hundred pediatric cancer patients.

Genomics and Pathology Services (GPS)

Genomics and Pathology Services (GPS) is a clinical genomics laboratory at Washington University School of Medicine in St. Louis and is a collaborative initiative between the Department of Pathology & Immunology and the Department of Genetics. Their CAP-accredited, CLIA-certified laboratories deliver clinically validated testing supported by extensive clinical and genomic experience and advanced technologies.

GPS’ clinical genomic tests improve patient care by enabling personalized medicine. Flagship genomic tests employ next-generation sequencing and return genomic intelligence across multiple key disease-relevant genes to drive treatment decisions. Sequencing results are interpreted by board certified pathologists and clinical geneticists; and variants are categorized by medical significance in a concise clinical report.

These results help physicians stratify disease subtypes and identify the best patient treatment strategies. The clinical report returned to the ordering physician contains expert clinical interpretations that pertain to the clinical diagnosis and the genetic variants identified in a patient. This allows for rapid patient management decisions to be made by the treating physician.

GPS has done solid tumor gene sequencing of 65 genes with clinical importance in a wide range of different types of cancer: adenocarcinomas, squamous cell carcinomas, gliomas, sarcomas and melanomas. Indications for testing include cancer cases in early stage disease where a mutational profile can affect diagnosis or disease stratification, prognosis, or treatment options. For late stage cancers, the test is designed to evaluate options for alternative treatments, including targeted therapies.

Another gene set deciphered is the hematopoietic (blood cancers) disorders gene set: sequencing of 54 genes with clinical importance in myeloid, lymphoid and mixed leukemias. It also includes genes that can help establish diagnosis and prognosis for pre-leukemic syndromes. Indications for testing include myelodysplastic and suspected cancer where a mutational profile from multiple genes has implications for diagnosis or disease stratification, prognosis, or treatment options. For leukemias, the test is designed to evaluate options for therapies targeting signaling pathways and DNA methylation

CNS Tumor Gene Set: this set of 24 genes has clinical importance in tumors of the central nervous system.

Melanoma Gene Set: Thirty-three genes have been identified with clinical importance in melanomas.

Genetic testing in cancer provides information useful for diagnosis, prognosis (chance of recovery, based on extent of disease), and treatment selection. A single mutation may impact all of these areas. The vast majority of this clinically relevant information applies to the effects of isolated mutations, and the current challenge is to understand how recurrent isolated mutations behave in different combinations.

Diagnosis – There are long-standing examples of mutations or rearrangements that are considered diagnostic for a particular solid tumor.

Prognosis – Mutational profiles are important in disease typing and subtyping. For example, some mutations may indicate a poor prognosis in adenocarcinomas of the lung, colon and pancreas. Others might indicate a poor prognosis in breast cancer and certain brain cancers, but be associated with a better prognosis in endometrial cancers.

Treatment – there are now dozens of mutations that have been identified in certain cancers that indicate whether the tumor will be susceptible or resistant to different anti-cancer therapy. As the number of known variants in mutated genes grows, testing becomes a more powerful technology to manage patients with cancer.