This year about 74,000 people in the U.S. (76% of them men and half will be over the age of 73 years old) will be told by a doctor that they have cancer of the urinary bladder. With significant improvements in the treatment of this malignancy, about 550,000 of them remain alive today.
Bladder cancer begins in different types of cells found in the inner lining of the bladder, the flexible muscular organ that stores urine. Transitional cells, which stretch or shrink as the bladder fills or empties, account for 90% of bladder cancers in the United States. Less commonly (in 6-8% of U.S. bladder cancers), the cancer begins in squamous cells that may form in response to irritation or infection that has lasted a long time. Adenocarcinoma begins in cells that make mucous and accounts for only about 2% of U.S. bladder cancers. Adenocarcinoma of the bladder is also believed to be a result of long-lasting irritation or inflammation.
If the cancer stays in the lining of the bladder, it is called superficial bladder cancer. Sometimes, though, transitional cell cancer spreads through the lining and breaks into the muscular wall beneath it or spreads to nearby organs and lymph nodes. In this case it is known as invasive bladder cancer.
Bladder cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, bladder cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the blood stream and go to other places in the body. In these distant places, the bladder cancer cells cause secondary (metastatic) tumors to grow, in the bones, for example. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a lymph node and a pathologist inspects it under a microscope. Several kinds of imaging can also be performed to determine if bladder cancer has spread. These include CT scans, MRI, chest x-rays and bone scans.
Source: National Cancer Institute, 2012
This year about 74,000 people in the U.S. (76% of them men and half will be over the age of 73 years old) will be told by a doctor that they have cancer of the urinary bladder. With significant improvements in the treatment of this malignancy, about 550,000 of them remain alive today.
Bladder cancer begins in different types of cells found in the inner lining of the bladder, the flexible muscular organ that stores urine. Transitional cells, which stretch or shrink as the bladder fills or empties, account for 90% of bladder cancers in the United States. Less commonly (in 6-8% of U.S. bladder cancers), the cancer begins in squamous cells that may form in response to irritation or infection that has lasted a long time. Adenocarcinoma begins in cells that make mucous and accounts for only about 2% of U.S. bladder cancers. Adenocarcinoma of the bladder is also believed to be a result of long-lasting irritation or inflammation.
If the cancer stays in the lining of the bladder, it is called superficial bladder cancer. Sometimes, though, transitional cell cancer spreads through the lining and breaks into the muscular wall beneath it or spreads to nearby organs and lymph nodes. In this case it is known as invasive bladder cancer.
Bladder cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, bladder cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the blood stream and go to other places in the body. In these distant places, the bladder cancer cells cause secondary (metastatic) tumors to grow, in the bones, for example. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a lymph node and a pathologist inspects it under a microscope. Several kinds of imaging can also be performed to determine if bladder cancer has spread. These include CT scans, MRI, chest x-rays and bone scans.
Source: National Cancer Institute, 2012
CLICK IMAGE FOR MORE INFORMATIONThe IDH1 gene encodes an enzyme called isocitrate dehydrogenase 1, found in the compartment of cells called the cytoplasm. This enzyme is normally involved in the transfer of energy from one molecule to another during certain biochemical reactions within the cell.
Mutations involving the IDH1 gene have been found in various cancers, including Acute Myeloid Leukemia (AML), intrahepatic bile duct cancers (Cholangiomas), Chondrosarcomas, and specific brain tumors (gliomas and glioblastomas). These alterations cause the amino acid (protein building block) arginine to be replaced by a different amino acid at a key position in the long chain of amino acids that make up this protein. The change in amino acid sequence alters the structure of the protein, resulting in loss of its normal function. Instead of its' normal metabolic product, the mutated IDH1 produces a new metabolite, R (-)-2-hydroxyglutarate, also called 2-HG. 2HG inhibits Tet and KGM enzymes, which alter the organization of DNA and disrupt normal gene expression patterns. These changes contribute directly to the development of cancer.
Tumor mutation profiling performed clinically at the MGH Cancer Center has identified the highest incidence of IDH1 mutations in brain tumors called gliomas (50-60%) and glioblastomas (~10%), cholangiocarcinomas (18-25%), chondrosarcomas, and Acute Myeloid Leukemia (5-10%).
The IDH1 gene encodes for the metabolic enzyme isocitrate dehydrogenase 1. This enzyme is located in the cytoplasm and peroxisomes of cells, and normally functions to catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, with the production of NADPH.
Recurrent mutations in IDH1 occur primarily at codon 132. These mutations result in decreased normal enzymatic activity, while conferring neomorphic activity that produces the oncometabolite R(-)-2-hydroxyglutarate (2HG) as the end-product. Levels of 2HG can accumulate dramatically in IDH1-mutant tumors and this is thought to promote tumorigenesis by competitively inhibiting the activity of a number of dioxygenases. The net effect appears to involve the promotion of gene silencing through hypermethylation of DNA and histones, as well as the activation of the hypoxia-inducible factor signaling pathway.
Tumor genotype testing performed clinically at the MGH Cancer Center has identified the highest incidence of IDH1 mutations in low-grade gliomas (50-60%), glioblastomas (~10%), cholangiocarcinomas (18-25%), chondrosarcomas, and acute myeloid leukemias (5-10%).
PubMed ID's
22234630,
22180306IDH mutations are rare in bladder cancers, though they are found in a small percentage of bladder cancers.
IDH mutations are rare in bladder cancers, though they are found in a small percentage of bladder cancers.
The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit
http://www.massgeneral.org/cancer/news/faq.aspx or contact the Cancer Center.