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Chapter 19: Problem 7

Compare familial and sporadic retinoblastomas in terms of genetics and age of onset. Is it possible to distinguish between these two using genetic tests? Consider the number of mutations required, loss of heterozygosity, and the two-hit hypothesis.

Short Answer

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Short Answer: Familial retinoblastoma is inherited and has an earlier age of onset, while sporadic retinoblastoma occurs due to random mutations in the RB1 gene with a later age of onset. Familial retinoblastoma involves one germline and one somatic mutation, whereas sporadic retinoblastoma involves two somatic mutations. Genetic tests can differentiate between the two by identifying germline mutations; however, negative tests do not completely rule out familial retinoblastoma.

Step by step solution

01

Understanding Familial and Sporadic Retinoblastomas

Familial retinoblastoma is an inherited form of the disease, which means it runs in families. It occurs when one of the parents carries a mutated RB1 gene and passes it to their child. Sporadic retinoblastoma, on the other hand, is not inherited and doesn't run in families. It happens due to random mutations in the RB1 gene, which occur in the retinal cells of the developing eye.
02

Differences in Genetics

In familial retinoblastoma, the first "hit" or mutation occurs in the germline (hereditary) cells, which means that it is present in all the cells of the individual. In sporadic retinoblastoma, both "hits" or mutations occur in the somatic (non-heritable) cells, specifically in the retinal cells. In both cases, the loss of function in the RB1 gene leads to the development of retinoblastoma.
03

Differences in Age of Onset

Familial retinoblastoma usually has an earlier age of onset compared to sporadic retinoblastoma. Children with the familial form of the disease are often diagnosed within the first year of life, while sporadic cases are typically diagnosed between the ages of 1 and 4.
04

Loss of Heterozygosity and the Two-Hit Hypothesis

Loss of heterozygosity (LOH) occurs when both copies of a gene are inactivated due to a mutation or the loss of a chromosome. The two-hit hypothesis of retinoblastoma suggests that both copies of the RB1 gene must be inactivated for the formation of a retinoblastoma tumor. In familial retinoblastoma, the first "hit" is inherited from one parent, while the second "hit" must occur in the retinal cells to give rise to a tumor. In sporadic retinoblastoma, both "hits" must occur in the retinal cells independently.
05

Differentiating Between Familial and Sporadic Retinoblastomas with Genetic Tests

Yes, it is possible to distinguish between familial and sporadic forms of retinoblastoma using genetic tests. By analyzing the DNA of tumor cells, genetic tests can identify the presence of a germline mutation in the RB1 gene, which indicates a familial case. A positive genetic test for a germline mutation can provide evidence for a familial form of retinoblastoma, while the absence of a germline mutation suggests sporadic retinoblastoma. However, negative genetic tests do not completely rule out the possibility of familial retinoblastoma, as there could be other genetic factors involved that are not detected by the test.

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Most popular questions from this chapter

Describe the steps by which the \(p 53\) gene responds to DNA damage and/or cellular stress to promote cell-cycle arrest and apoptosis. Given that \(p 53\) is a recessive gene and is not located on the X chromosome, why would people who inherit just one mutant copy of a recessive tumor-suppressor gene be at higher risk of developing cancer than those without the recessive gene?

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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 \(13: 445-455\) ). (a) How might hypermethylation of the \(p 53\) gene promoter influence tumorigenesis? (b) Knowing that tumors release free DNA into certain surrounding body fluids through necrosis and apoptosis (Kloten et al., 2013. Breast Cancer Res. \(15(1): \mathrm{R} 4\) ), outline 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.

In this chapter, we focused on cancer as a genetic disease, with an emphasis on the relationship between cancer, the cell cycle, and DNA damage, as well as on the multiple steps that lead to cancer. (a) How do we know that malignant tumors arise from a single cell that contains mutations? (b) How do we know that cancer development requires more than one mutation? (c) How do we know that cancer cells contain defects in DNA repair?

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