Researchers have identified the gene mutation responsible for basal cell carcinoma, the skin tumor that is the most common form of cancer in humans.
In reports published Friday in the journals Science and Cell, scientists say the mutation of a gene called "patched" allows the uncontrolled growth of tumor cells in the skin, causing a type of cancer that strikes 750,000 Americans annually but is seldom lethal.The researchers also found that the same gene mutation, when inherited, is the cause of basal cell nevus syndrome, or BCNS, a rare disorder that causes a variety of symptoms, including skin cancers, abnormal bone development, jaw cysts and spinal defects. BCNS affects between 1 in 57,000 and 1 in 164,000 people.
A California team led by Matthew P. Scott, a Howard Hughes Medical Institute researcher at Stanford University, identified the patched gene in the fruit fly and found that its mutation caused developmental problems in the insect.
Guided by the fruit fly gene pattern, Scott's group located the patched gene in mice and then in men.
Scott learned that Dr. Ervin H. Epstein Jr., a University of California, San Francisco, dermatologist, was leading a search for the human gene that causes BCNS. He contacted Epstein and suggested that patched gene may be the BCNS gene.
The two groups combined their efforts and confirmed that people with BCNS did, in fact, inherit the mutated patched gene.
They also found that the same gene was present in basal cell carcinoma tumors, the skin cancer caused by excessive exposure to sunlight. When non-tumor cells in patients with skin cancer were tested, the researchers found a normal patched gene. This supported the idea that ultraviolet rays from the sun cause the mutation that leads to skin cancer, the researchers said.
The Scott and Epstein study is published in Science.
An international team of researchers led by Allen E. Bale of Yale University also identified the patched gene and related it to both BCNS and to the more common basal cell carcinoma. This research is in the journal Cell.
Discovery that the patched gene regulates embryo development before birth and cell division later in life suggests that it may be fundamental in the understanding of cancer, said Dr. Richard Klausner, director of the National Cancer Institute.
"It's going to tell us a great deal about cancer and human development," he said in a statement.
Scott said that patched has apparently been a part of the genetic pattern of life for millions of years because it is present virtually unchanged in fruit fly, mouse and human, creatures separated by eons of evolution.
"Some of the genes we study are doing the same thing in human and in fruit fly," said Scott.
Fruit flies are used in research because they hatch, reproduce and die within days, allowing genetic study of many generations within a short time.
Pairs of the patched gene regulate cell growth by helping to turn off another gene, called Hedgehog, that triggers cell division. People who inherit one mutated copy of the patched gene have birth defects, mostly affecting the bones. Two mutated or missing patched genes can lead to rapid development of skin cancer.