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GEN124 Genetics:Mutation Spectrum in Smokers and Smoking Lung Cancer

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GEN124 Genetics

Question:

Guide to the Literature Review Assignment

Task: Literature review

This literature review will require you to submit a written article on your interpretations and understanding of a research paper. A paper on genetics and molecular biology will be selected by the module coordinator for you to review in this assignment.

Writing the review paper

1. An abstract (200 words maximum) written in your own words, that describe the main scientific findings in the paper using clear language. This abstract is supposed to quickly reveal the importance of the research done in the paper, and attract others to read your literature review. An abstract should include:

A. 2-3 sentences on field of research, what problems it’s trying to address, and why these problems are important
B. 3-4 sentences highlighting main experimental findings of article
C. 1-2 sentences on significance of these findings and future outcomes

2. A background description of the field of research your research article is covering. This involves answering questions like:

A. What are the main research questions scientists are trying to answer in this field?
B. Why is this field of research important?
C. What key findings have been made so far?

3. Detailed description of main experimental findings in the research article.

You should include figures from your research paper that directly show the results of experiments performed (make sure these figures are properly referenced!). You will not have enough space to go over all of the results in the paper in this literature review, so it is important you pick out the major experimental findings only and discuss them in detail. 

4. Discussion of the significance and future outcomes of the scientific findings made in your research article. You need to interpret the experiments in your research article, compare these results to previously published literature.

Mutation Spectrum in Smokers and Never Smoking Lung Cancer Patients

Introduction

Lung cancer is one of the most common types of cancers, and due to its aggressiveness, this disease is also positioned as the most deadly cancer disease worldwide (Ferlay et al., 2015). Lung cancers can be divided into small-cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC), consisting of adenocarcinomas (AC), squamous cell carcinomas (SCC), and large cell carcinomas (LCC) (Travis, 2014). The TP53 gene has been known as a tumor suppressor since the 1990s (Malkin et al., 1990). The TP53 protein is involved in regulation of essential cell activities, like the cell cycle, cell death, cell differentiation, DNA repair, and formation of blood vessels (Lane and Levine, 2010), and has been called “the guardian of the genome.” These pathways are also involved in processes required to become a cancerous cell, and comprises several of the hallmarks of cancer, such as sustained angiogenesis and evading apoptosis (Hanahan and Weinberg, 2011).

Since the first discovery of the protein, much effort has been invested to reveal the spectrum of function for this protein and the related pathways. Still, details about the consequences of the different types of TP53 mutations for cancer patients are largely unknown. Research has shown that mutations in the TP53 gene are frequent in almost all types of cancers (Hollstein et al., 1991), and are present in approximately 50% of all NSCLC (Toyooka et al., 2003). Numerous of these mutations may be due to smoking history, and a frequent transversion, GC to TA, is strongly correlated to exposure to carcinogens found in tobacco (Pfeifer et al., 2002).

Materials and Methods

The patients in this study were diagnosed with operable NSCLC, and underwent curatively intended surgical resection at Rikshospitalet, Oslo University Hospital, Norway during the period 2006–2011. Clinical data were obtained from questionnaires, medical journals, and histology reports, and follow up information were reported from the patient’s local hospital. The project was approved by the institutional review board and the Regional Ethics Committee (S-06402b). The participants in our study received oral and written information and signed a written consent form before entering the project.

DNA Extraction

DNA was extracted from tumor tissue using Maxwell R 16 DNA Purification Kits and a Maxwell R 16 instrument. The procedure was performed according to technical manual, Literature # TM2841 . DNA from blood was isolated using the Master Pure DNA purification Kit for blood according to the DNA Purification Protocol2 .

EGFR Mutation Analyses

Tumor specimens were analyzed for EGFR-mutations at Unit of Molecular Pathology, Department of Pathology, Oslo University Hospital. The mutation analysis of EGFR exons 18–21 was performed by real-time PCR using TheraScreen EGFR mutation kit (DxS, Manchester, UK), which analyses 28 of the most commonly occurring genetic changes.

Mutation Classification

The TP53 mutations recorded in this study were classified according to their predicted effect on the protein. The different categories were silent, missense in non-DBM, missense in DBM, non-sense, splice, frameshift, and inframe, as previously described (Olivier et al., 2006). For some of the analyses, the categories missense (non-DBM and DBM) and non-missense (frameshift, splice, non-sense, and inframe) were used.

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