19. Cancer Genetics

Cancer Mutations

19. Cancer Genetics

Cancer Mutations

2:05 minutes

Problem 28c

Textbook Question

The table in this problem summarizes some of the data that have been collected on mutations in the BRCA1 tumor-suppressor gene in families with a high incidence of both early-onset breast cancer and ovarian cancer.

Although the mutations listed in the table are clearly deleterious and cause breast cancer in women at very young ages, each of the kindred groups had at least one woman who carried the mutation but lived until age 80 without developing cancer. Name at least two different mechanisms (or variables) that could underlie variation in the expression of a mutant phenotype, and propose an explanation for the incomplete penetrance of this mutation. How do these mechanisms or variables relate to this explanation?

Verified step by step guidance

Step 1: Understand the concept of incomplete penetrance. Incomplete penetrance occurs when individuals with a genetic mutation do not exhibit the associated phenotype. This means that not all carriers of a deleterious mutation will develop the disease, as seen in the BRCA1 mutation carriers who lived until age 80 without developing cancer.

Step 2: Identify potential mechanisms or variables that could influence the expression of the mutant phenotype. Two common mechanisms include: (1) Environmental factors, such as lifestyle choices (e.g., diet, exercise, exposure to carcinogens) that may mitigate or exacerbate the risk of developing cancer, and (2) Genetic modifiers, which are other genes that interact with the BRCA1 mutation and influence its phenotypic expression.

Step 3: Propose an explanation for incomplete penetrance based on environmental factors. For example, a woman carrying the BRCA1 mutation may have avoided environmental triggers such as smoking or excessive alcohol consumption, which are known to increase cancer risk. Additionally, she may have engaged in protective behaviors like maintaining a healthy diet rich in antioxidants or undergoing regular medical screenings.

Step 4: Propose an explanation for incomplete penetrance based on genetic modifiers. Certain genetic variants in other genes may suppress the deleterious effects of the BRCA1 mutation. For instance, genes involved in DNA repair pathways might compensate for the loss of BRCA1 function, reducing the likelihood of cancer development.

Step 5: Relate these mechanisms to the observed variation in phenotype. Environmental factors and genetic modifiers can act independently or synergistically to influence the expression of the BRCA1 mutation. This explains why some individuals with the mutation develop cancer at a young age, while others remain unaffected even into old age. These mechanisms highlight the complexity of gene-environment interactions and the role of genetic background in determining disease risk.

Verified video answer for a similar problem:

This video solution was recommended by our tutors as helpful for the problem above

Video duration:

Was this helpful?

Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

BRCA1 Gene Function

The BRCA1 gene is crucial for maintaining genomic stability and repairing DNA breaks. It encodes a protein that plays a significant role in the homologous recombination repair pathway, which fixes double-strand breaks in DNA. Mutations in BRCA1 can lead to a loss of function, increasing the risk of breast and ovarian cancers. Understanding its normal function helps explain how mutations can lead to cancer predisposition.

Incomplete Penetrance

Incomplete penetrance refers to the phenomenon where not all individuals with a specific genotype express the expected phenotype. In the context of BRCA1 mutations, some carriers may not develop cancer due to various factors, such as environmental influences, lifestyle choices, or the presence of other genetic modifiers. This concept is essential for understanding why some individuals with deleterious mutations remain unaffected.

Modifier Genes

Modifier genes are additional genes that can influence the expression of a primary gene's phenotype. In the case of BRCA1 mutations, these modifier genes may enhance or suppress the risk of developing cancer. They can interact with the BRCA1 mutation, affecting cellular pathways and responses to DNA damage, thereby contributing to the variability in cancer risk among mutation carriers.

Watch next

Master Cancer Mutations with a bite sized video explanation from Kylia

Start learning

Related Videos

Related Practice

Textbook Question

Mutations in tumor-suppressor genes are associated with many types of cancers. In addition, epigenetic changes (such as DNA methylation) of tumor-suppressor genes are also associated with tumorigenesis [Otani et al. (2013). Expert Rev Mol Diagn 13:445 455].

Knowing that tumors release free DNA into certain surrounding body fluids through necrosis and apoptosis, Kloten et al. [(2013). Breast Cancer Res. 15(1):R4] outlines an experimental protocol for using human blood as a biomarker for cancer and as a method for monitoring the progression of cancer in an individual.

394

views

Textbook Question

A study by Bose and colleagues (1998). Blood 92:3362-3367] and a previous study by Biernaux and others (1996). Bone Marrow Transplant 17:(Suppl. 3) S45–S47] showed that BCR-ABL fusion gene transcripts can be detected in 25 to 30 percent of healthy adults who do not develop chronic myelogenous leukemia (CML). Explain how these individuals can carry a fusion gene that is transcriptionally active and yet does not develop CML.

441

views

Textbook Question

What evidence indicates that mutations in human DNA mismatch repair genes are related to certain forms of cancer?

413

views

Textbook Question

Those who inherit a mutant allele of the RB1 tumor-suppressor gene are at risk for developing a bone cancer called osteosarcoma. You suspect that in these cases, osteosarcoma requires a mutation in the second RB1 allele, and you have cultured some osteosarcoma cells and obtained a cDNA clone of a normal human RB1 gene. A colleague sends you a research paper revealing that a strain of cancer-prone mice develops malignant tumors when injected with osteosarcoma cells, and you obtain these mice. Using these three resources, what experiments would you perform to determine:

(a) Whether osteosarcoma cells carry two RB1 mutations

(b) Whether osteosarcoma cells produce any pRB protein

378

views

Textbook Question

The table in this problem summarizes some of the data that have been collected on mutations in the BRCA1 tumor-suppressor gene in families with a high incidence of both early-onset breast cancer and ovarian cancer.

Examine the types of mutations that are listed in the table, and determine if the BRCA1 gene is likely to be a tumor-suppressor gene or an oncogene.

332

views

Textbook Question

Note the coding effect of the mutation found in kindred group 2082. This results from a single base-pair substitution. Draw the normal double-stranded DNA sequence for this codon (with the 5' and 3' ends labeled), and show the sequence of events that generated this mutation, assuming that it resulted from an uncorrected mismatch event during DNA replication.

410

views

Textbook Question

Skin cancer carries a lifetime risk nearly equal to that of all other cancers combined. Following is a graph [modified from K. H. Kraemer (1997). Proc. Natl. Acad. Sci. (USA) 94:11 14] depicting the age of onset of skin cancers in patients with or without XP, where the cumulative percentage of skin cancer is plotted against age. The non-XP curve is based on 29,757 cancers surveyed by the National Cancer Institute, and the curve representing those with XP is based on 63 skin cancers from the Xeroderma Pigmentosum Registry.

Explain why individuals with XP show such an early age of onset.

397

views

Textbook Question

Provide an overview of the information contained in the graph.

553

views

Show more practices