Developing a method to study the effect of germline variants and somatic mutations in breast cancer patients on mRNA splicing
(2023) BINP52 20222Degree Projects in Bioinformatics
- Abstract
- Analysis of alternative splicing has provided valuable information for multiple types of cancer, including breast cancer in recent years. Alternative splicing has been suggested to be one of the hallmarks for cancer, as dysregulation of the normal splicing process governs many aspects of cancer cell biology. For several genes previously associated with cancer, specific variants and their effect on alternative splicing have been investigated, but there is much left to explore. This project combines a genome-wide analysis of alternative splicing and genetic variation. Using a custom developed pipeline, it investigates the relationship between genetic variants and alternative splicing events found in breast cancer patients. Are there variants... (More)
- Analysis of alternative splicing has provided valuable information for multiple types of cancer, including breast cancer in recent years. Alternative splicing has been suggested to be one of the hallmarks for cancer, as dysregulation of the normal splicing process governs many aspects of cancer cell biology. For several genes previously associated with cancer, specific variants and their effect on alternative splicing have been investigated, but there is much left to explore. This project combines a genome-wide analysis of alternative splicing and genetic variation. Using a custom developed pipeline, it investigates the relationship between genetic variants and alternative splicing events found in breast cancer patients. Are there variants that affect the frequency for an alternative splicing event in these patients? And if so, how do the genotypes at that variant location affect the frequencies? Answering these questions will teach us more about tumour biology and potential genes affecting tumour growth and occurrence. It would also help us improve prediction of effects of variants in f.e. genetic testing. We show in this report the pipeline developed to investigate alternative splicing and variants found in breast cancer patients based on RNA-Seq data. Results for 10,699 genes and 3455 samples, give us an initial idea on how event and variant pairs can be identified and a list of significant pairs, which can be investigated further. (Less)
- Popular Abstract
- The Splice of Life: How Genetic Variants affect Splicing in Breast Cancer
Each person has their own unique set of genetic material (DNA), which is why we all look different and are more or less likely to become sick with a specific disease. In tumour cells occur even further mutations and some of these help the cancer grow or spread.
To create a protein, messenger RNA (mRNA) is translated. This mRNA comes from first being transcribed as a copy from DNA and then being edited by a cut and paste process called splicing. How it is cut and reassembled can vary, potentially creating many different mRNA from the same DNA sequence. This is called alternative splicing and affects most genes found in humans. This is important for the function... (More) - The Splice of Life: How Genetic Variants affect Splicing in Breast Cancer
Each person has their own unique set of genetic material (DNA), which is why we all look different and are more or less likely to become sick with a specific disease. In tumour cells occur even further mutations and some of these help the cancer grow or spread.
To create a protein, messenger RNA (mRNA) is translated. This mRNA comes from first being transcribed as a copy from DNA and then being edited by a cut and paste process called splicing. How it is cut and reassembled can vary, potentially creating many different mRNA from the same DNA sequence. This is called alternative splicing and affects most genes found in humans. This is important for the function of normal cells but can also influence cancer biology.
In recent years, we have learned that alternative splicing can give us information about different cancer types, including breast cancer. Tumour – specific splice variants could potentially even become targets for treatment of cancer. In breast cancer patients, mRNA splicing can be influenced by both normal genetic variations as well as mutations in the tumour. This can change how proteins function and ultimately alter cell behaviour. The aim of this project is to investigate the relationship between variants and mutations in breast cancer patients and alternative splicing of mRNA. We have developed a method to find variants and mutations that can change splicing patterns.
The method consists of three main steps: First, genetic variants are found in patient data and genotypes are determined. Genotype refers to an organism’s DNA sequence at each position in the genome, where we have two copies of most genes that were passed down from parent to offspring. Since this method works with patient data from RNA, we can only make predictions for genes which are transcribed to RNA. The next step is to identify splicing events and then score them based on how often they are found in each patient. Lastly, we do statistical testing for each pair of variant and splice event found in the same gene to see if there is a difference in scores between genotypes.
Our method was applied to data for breast tumours from 3455 patients enrolled in the SCAN-B study. For these patients 10,699 genes were analysed. We identified 250’000 pairs of variants and splice events with a significant test result. This gives us an initial idea of the relationship between genetic variants and alternative splicing as well as a list of interesting pairs for further research.
Master’s Degree Project in Bioinformatics 60 credits 2023
Department of Biology, Lund University
Advisor: Helena Persson
Department of Clinical Sciences Lund, Oncology (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9114535
- author
- Karlsson-Müller, Mirjam
- supervisor
- organization
- course
- BINP52 20222
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9114535
- date added to LUP
- 2023-05-15 13:40:45
- date last changed
- 2023-05-15 13:40:45
@misc{9114535,
abstract = {{Analysis of alternative splicing has provided valuable information for multiple types of cancer, including breast cancer in recent years. Alternative splicing has been suggested to be one of the hallmarks for cancer, as dysregulation of the normal splicing process governs many aspects of cancer cell biology. For several genes previously associated with cancer, specific variants and their effect on alternative splicing have been investigated, but there is much left to explore. This project combines a genome-wide analysis of alternative splicing and genetic variation. Using a custom developed pipeline, it investigates the relationship between genetic variants and alternative splicing events found in breast cancer patients. Are there variants that affect the frequency for an alternative splicing event in these patients? And if so, how do the genotypes at that variant location affect the frequencies? Answering these questions will teach us more about tumour biology and potential genes affecting tumour growth and occurrence. It would also help us improve prediction of effects of variants in f.e. genetic testing. We show in this report the pipeline developed to investigate alternative splicing and variants found in breast cancer patients based on RNA-Seq data. Results for 10,699 genes and 3455 samples, give us an initial idea on how event and variant pairs can be identified and a list of significant pairs, which can be investigated further.}},
author = {{Karlsson-Müller, Mirjam}},
language = {{eng}},
note = {{Student Paper}},
title = {{Developing a method to study the effect of germline variants and somatic mutations in breast cancer patients on mRNA splicing}},
year = {{2023}},
}