Chapter 12, Problem 15MC

You are in charge of a new gene therapy clinic. Two cases have been referred to you for review and possible therapy. Case 1. A mutation in the promoter of a proto-oncogene causes the gene to make too much of its normal product, a receptor protein that promotes cell division. The uncontrolled cell division has caused cancer. Case 2. A mutation in an exon of a tumor-suppressor gene makes this gene nonfunctional. The product of this gene normally suppresses cell division. The mutant gene cannot suppress cell division, and this has led to cancer. What treatment options can you suggest for each case?

Should he go ahead and enroll on the chance that he would receive the DNA vaccine and that it would be more effective than chemotherapy? Bruce and his parents moved to a semi-tropical region of the United States when he was about 3 years old. He loved to be outside year-round and swim, surf, snorkel, and play baseball. Bruce was fair-skinned, and in his childhood years, was sunburned quite often. In his teen years, he began using sunscreens, and although he never tanned very much, he did not have the painful sunburns of his younger years. After graduation from the local community college, Bruce wanted an outdoor job and was hired at a dive shop. He took people out to one of the local reefs to snorkel and scuba dive. He didnt give a second thought to sun exposure because he used sunscreen. His employer did not provide health insurance, so Bruce did not go for annual checkups, and tried to stay in good health. In his late 20s, Bruce was injured trying to keep a tourist from getting caught between the dive boat and the dock. He went to an internist, who treated his injury and told Bruce he was going to give him a complete physical exam. During the exam, the internist noticed a discolored patch of skin on Bruces back. She told him that she suspected Bruce had skin cancer and referred him to a dermatologist, who biopsied the patch. At a follow-up visit, Bruce was told that he had melanoma, a deadly form of skin cancer. Further testing revealed that the melanoma had spread to his liver and his lungs. The dermatologist explained that treatment options at this stage are limited. The drugs available for chemotherapy have only temporary effects, and surgery is not effective for melanoma at this stage. The dermatologist recommended that Bruce consider entering a clinical trial that was testing a DNA vaccine for melanoma treatment. These vaccines deliver DNA encoding a gene expressed by the cancer cells to the immune system. This primes the immune system to respond by producing large quantities of antibodies that destroy melanoma cells wherever they occur in the body. A clinical trial using one such DNA vaccine was being conducted at a nearby medical center, and Bruce decided to participate. At the study clinic, Bruce learned that he would be in a Phase Ill trial, comparing the DNA vaccine against the standard treatment, which is chemotherapy, and that he would be randomly assigned to receive either the DNA vaccine or the chemotherapy. He was disappointed to learn this. He thought he would be receiving the DNA vaccine.

Mike was referred for genetic counseling because he was concerned about his extensive family history of colon cancer. That family history was highly suggestive of hereditary nonpolyposis colon cancer (HNPCC). This predisposition is inherited as an autosomal dominant trait, and those who carry the mutant allele have a 75% chance of developing colon cancer by age 65. Mike was counseled about the inheritance of this condition, the associated cancers, and the possibility of genetic testing (on an affected family member). Mikes aunt elected to be tested for one of the genes that may be altered in this condition and discovered that she did have an altered MSH2 gene. Other family members are in the process of being tested for this mutation. Seventy-five percent of people who carry the mutant allele will get colon cancer by age 65. This is an example of incomplete penetrance. What could cause this?