Oncogenes & tumour suppressor genes

A study of cells from a human embryo found that 2.66 × 10^–7 % of the genome of one cell had changed due to mutation.

You can assume that:

• the genome contains 3 × 10⁹ nucleotides

• the mean rate of mutation is 1.14 mutations per cell cycle

• the cell cycle lasts 24 hours.

Use this information to calculate the age of the embryo in days.

Show your working.

The genome of the bacterium Escherichia coli is approximately 4.6 million base pairs in length and contains around 4000 genes.

The analysis of the genome of E. coli allows the proteome to be determined more easily than that of eukaryotes.

Explain why.

Determining the proteomes of bacteria has helped provide protection for individuals and populations against some infectious diseases.

Explain how.

Scientists investigated the relationship between one type of variable number tandem repeat (VNTR) and the risk of breast cancer occurring in women.

The scientists determined the risk of breast cancer occurring in women:

• with 2, 3 or 4 repeats of the VNTR

• without the VNTR.

They calculated the odds ratio (OR) of breast cancer occurring with 2, 3 or 4 repeats of the VNTR.

An OR is a measure of how strongly an outcome is associated with a risk factor.

The OR formula is:

risk of breast cancer occurring with the VNTR: risk of breast cancer occurring without the VNTR

Table 5 shows the scientists’ results.

A student concluded that the number of repeats of the VNTR is associated with the risk of breast cancer occurring in women.

Evaluate the student’s conclusion.

The KRAS gene codes for a protein called K-Ras. The protein relays signals from outside a cell to a cell’s nucleus, stimulating cell division. An alteration in the KRAS gene produces an oncogene which can cause a tumour to develop.

Suggest and explain how an alteration in the KRAS gene can cause a tumour to develop.

Alterations in the KRAS gene can cause colorectal cancer (CRC). Scientists investigated the survival time of the following three groups of CRC patients who had type II diabetes.

Group A – received no drug to treat type II diabetes Group B – received the drug metformin to treat type II diabetes Group C – received a combination of drugs (including metformin) to treat type II diabetes

The scientists used a statistical test to compare the survival time of these patients with CRC patients with no history of type II diabetes.

Table 1 shows some of the results obtained by the scientists.

Using the information provided, what can you conclude about the effects of type II diabetes and the different drug treatments on the survival time of CRC patients?

BRCA1 and BRCA2 are human genes that code for tumour suppressor proteins. Mutations in BRCA1 and BRCA2 can cause cancer (lines 1–2). Explain how.

Genetic testing, using DNA from saliva, can screen for all known harmful mutations in both genes (lines 5–6). Describe how this DNA could be screened for all known harmful mutations in both genes.

Effective treatment of ER-positive breast cancers often involves the use of drugs which have a similar structure to oestrogen (lines 9–10).

Suggest and explain how these drugs are an effective treatment of ER-positive breast cancers.

Blood tests can be used to test for cancers (line 11). However, the results of blood tests may not be conclusive when testing for prostate cancer. Explain why.

Treatment with drugs might be able to reverse the epigenetic changes that cause cancers (lines 16–17). Suggest and explain how.

Myelodysplastic syndromes (MDS) are a group of malignant cancers. In MDS, the bone marrow does not produce healthy blood cells.

Haematopoietic stem cell transplantation (HSCT) is one treatment for MDS. In HSCT, the patient receives stem cells from the bone marrow of a person who does not have MDS. Before the treatment starts, the patient’s faulty bone marrow is destroyed.

For some patients, HSCT is an effective treatment for MDS.

Explain how.

MDS can develop from epigenetic changes to tumour suppressor genes. In some patients, the drug AZA has reduced the effects of MDS. AZA is an inhibitor of DNA methyltransferases. These enzymes add methyl groups to cytosine bases.

Suggest and explain how AZA can reduce the effects of MDS in some patients.

Scientists investigated the effectiveness of AZA in patients with MDS. A total of 360 patients were randomised in the ratio of 1:1 to receive AZA or conventional drugs (control).

Figure 6 shows the scientists’ results.

The control patients were treated with conventional drugs.

Give two reasons why.

Use Figure 6 and the information provided to calculate the difference in the number of patients surviving at 10 months after treatment with AZA compared with conventional drugs.

Testosterone is a steroid hormone that belongs to a group of male sex hormones called androgens.

Steroid hormones are hydrophobic.

Explain why steroid hormones can rapidly enter a cell by passing through its cell-surface membrane.

In the cytoplasm, testosterone binds to a specific androgen receptor (AR). An AR is a protein.

Suggest and explain why testosterone binds to a specific AR.

The binding of testosterone to an AR changes the shape of the AR. This AR molecule now enters the nucleus and stimulates gene expression.

Suggest how the AR could stimulate gene expression.

The gene that codes for the AR has a variable number of CAG repeats. Some studies have shown an association between the number of CAG repeats and the risk of developing prostate cancer.

Table 1 shows the results of a statistical test from one study.

What can you conclude from the data in Table 1 ?

In the UK in 2016, there were 525 048 deaths. Cancer caused 30.4% of all deaths. Throat cancer caused 5% of all deaths from cancer.

Calculate the mean number of people who died of throat cancer per month in 2016.

Show your working.

Increased methylation of the promoter region of a tumour suppressor gene causes one type of human throat cancer.

In this type of throat cancer, cancer cells are able to pass on the increased methylation to daughter cells. The methylation is caused by an enzyme called DNMT.

Scientists have found that a chemical in green tea, called EGCG, is a competitive inhibitor of DNMT. EGCG enables daughter cells to produce messenger RNA (mRNA) from the tumour suppressor gene.

Suggest how EGCG allows the production of mRNA in daughter cells.

The scientists investigated the effect of different amounts of EGCG on the growth rate of the throat cancer cells grown in vitro. Their results are shown in Figure 2.

Figure 2

This figure has been removed due to third-party copyright restrictions.

A reporter who reviewed all of this work concluded that drinking green tea could be a cure for cancer.

Suggest three reasons why his conclusion might not be valid.

There are different types of gene mutation.

Put a tick () in the box next to the statement which describes incorrectly the effect of the mutation in an exon of a gene.

Describe how alterations to tumour suppressor genes can lead to the development of tumours.

A type of malignant tumour cell divides every 8 hours.

Starting with one of these cells, how many tumour cells will be present after 4 weeks? Assume none of these cells will die.

Give your answer in standard form.

Name two enzymes involved in the semi-conservative replication of DNA.

Sometimes, damage occurs during DNA replication. One enzyme involved in repairing damage to DNA is called ATR.

ATR works as follows.

ATR phosphorylates other enzymes involved in repairing DNA.

ATR also phosphorylates substrates required to repair DNA.

When ATR phosphorylates other enzymes, these enzymes become able to bind to their substrates.

Use your knowledge of enzyme structure to suggest why.

The enzyme-catalysed reactions activated by ATR only occur if the substrates have been phosphorylated.

Use your knowledge of energy changes in enzyme-catalysed reactions to suggest why.

Sometimes, a mutagenic agent causes DNA to break. A different enzyme called ATM binds to the broken DNA. This leads to the activation of a protein coded for by a tumour suppressor gene. The effect of ATM binding is to stop cell division until DNA is repaired.

A mutation could result in a person having non-functional forms of the gene that produces ATM.

What can you predict about the possible effects of having a non-functional form of ATM?