What do your genes do?
Genes are short pieces of DNA that carry your traits—those things your parents pass on to you. Your genes have instructions that tell your cells what to do. Your genes can change over time, as you age.
A gene that changes is a mutation. It is a change that occurs in our DNA sequence. Mutations are either due to mistakes that occur when the cells divide and make copies of the DNA. Or as a result of contact with things in your environment. This can include exposure to smoking or certain chemicals. These mutations are not related to the genes that you inherit from your parents. With certain mutations, you may be more likely to get bladder cancer.
Bladder cancer has a high number of genetic mutations compared to other cancers. Many of these mutations are random. Their effect on tumor growth is unknown. Some mutations affect genes that are important for cell growth, survival, and DNA damage repair. Your doctor may want to find out if you have certain gene mutations.
How do your genes relate to bladder cancer treatments?
Researchers have found that specific medicines work well on certain mutations in bladder cancer tumor genes. Some of these mutations help your bladder cancer tumor to grow and survive. There may be drugs or combinations of medications that specifically target these mutation pathways that can slow a tumor’s growth. This has the potential to improve survival for patients.
While not the most common mutation, one of the most therapeutically important alterations is in the gene FGFR3. This gene has mutations in 13% of muscle invasive bladder cancers. Patients with this mutation may benefit from treatment with specific drugs. To identify the genetic alterations of a bladder cancer, a physician needs to evaluate 1) tumor tissue and 2) DNA that is present in the blood. In some cases, the genetic analysis also includes cell-free DNA that is circulating in the blood.
Does my bladder tumor have the same genes wherever it grows in my body?
There is a great deal of variability between mutations in different parts of a bladder cancer tumor. If the cancer has grown out of the bladder there may be differences in mutations between different sites of the urothelial cancer. There may even be important differences from the same tumor if sampled at different times.
For tumors in the bladder, ureter or renal pelvis, a prior biopsy may potentially be used. This would include a transurethral (TUR) or radical cystectomy specimen. If it has been more than 1 year, it may be necessary to obtain another biopsy to ensure the specimen is good quality and the mutations are accurate. If the cancer involves the lymph nodes or is outside of the bladder, a new biopsy or a sample of blood may be used.
Can I pass my gene mutations to my children?
In approximately 15% of patients, potentially important mutations occur throughout the body. These may pass from one generation to the next. Genetic testing identifies “germline” mutations in all stages and locations of bladder cancer. They include BRCA1, BRCA2, MSH2, CHEK2, and ERCC3. These alterations would have potentially critical implications to patients with bladder cancer, but also their siblings and children.
The Bladder Cancer Genome Atlas
The National Cancer Institute first published a comprehensive description of 131 patients with Stage II or greater muscle invasive bladder cancer (MIBC) in 2014. This genetic analysis created a molecular atlas or blueprint of bladder cancer called the “bladder cancer genome atlas,” and is free and publicly available for researchers, physicians and patients.
The Bladder Cancer Genomics Consortium
In an effort to further advance bladder cancer research, BCAN has launched the Bladder Cancer Genomics Consortium (BCGC). Learn more here.