The correct answer is A. The diagram demonstrates the structure of a thymine dimer, which results when UV radiation causes a covalent linkage between two adjacent thymine nucleotides on the same strand. An inability to repair this defect results in xeroderma pigmentosum, a rare inherited disorder characterized by extreme UV sensitivity, excessive freckling, early-onset skin cancer (basal cell carcinoma, squamous cell carcinoma, and malignant melanoma), and corneal ulceration with or without neurologic abnormalities. It is transmitted with an autosomal recessive pattern of inheritance and is due to mutations in XPA, XPB, XPC, XPD, XPE, XPF, XPG, and/or XPV genes.
None of the other answer choices are associated with mutations in nucleotide excision repair genes and UV-induced thymine dimers.
Colorectal adenocarcinoma (choice B) is a cancer of the intestinal epithelium lining the colon and rectum. This type of cancer accounts for more than 95% of colorectal cancers, and is commonly associated with mutations in the tumor suppressor genes APC and TP53, as well as activation of the oncogene KRAS.
Ductal carcinoma in situ (choice C) is the most common form of breast cancer, arising from epithelial cells of the mammary ductal system. These cancers commonly result from mutations in the BRCA1 or BRCA2 genes.
Hepatocellular carcinoma (choice D) is the most common malignancy of the liver, frequently associated with chronic viral hepatitis, dietary aflatoxin B1 exposure, and alcoholism. Mutations in TP53 are common.
Small cell carcinoma (choice E) is a type of highly malignant lung cancer. Approximately 15% of all lung cancers are small cell carcinomas, and occur almost exclusively in smokers. Mutations in several genes have been linked to this cancer, including TP53 and RB1.
This is a multi-step question.
What is the question asking?
You are asked to determine which of the following is most likely to develop in individuals with this disease.
What is the first step?
The first step is to determine what type of DNA damage is occurring. Looking at the figure, you can see two thymine bases linked to each other, representing the formation of thymine dimers within the DNA.
What is the next step?
The next step is to recall that thymine dimers are formed upon exposure of the DNA to ultraviolet light, which occurs during sun exposure.
What is the next step?
Next, recall that thymine dimers are repaired through a complex process known as nucleotide excision repair. You should then recall that mutations in any of the many proteins required for nucleotide excision repair will lead to xeroderma pigmentosum and an increased risk for the development of skin cancer including basal cell carcinoma (choice A).
Can other answers be eliminated?
Eliminate conditions that result from other mutations in DNA repair mechanisms:
- Colorectal adenocarcinoma (choice B) can result from mutations in APC or mismatch repair genes.
- Ductal carcinoma in situ (choice C), or breast cancer, can evolve due to mutations in genes involved in repairing double-strand breaks in DNA such as BRCA1 and BRCA2.
- Hepatocellular carcinoma (choice D) can result from mutations in the TP53 tumor suppressor gene.
- Small cell carcinoma (choice E) in the lung occurs most frequently in smokers and is due to mutations in TP53 and RB1.
What is the single best answer and why?
Basal cell carcinoma (choice A) is the best answer, as it results in patients with xeroderma pigmentosum from an inability to repair thymine dimers.
MedEssentials (4th Ed.): pp. 64, 451
First Aid (2019): pp. 40.1, 473.1
First Aid (2018): pp. 40.1, 469.1
First Aid (2017): pp. 37.1, 454.1
