Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients

Mitochondrial DNA (mtDNA) mutations, oxidative stress and resistance to cell deaths increase one’s risk for breast cancer. This study aims to identify the types of mtDNA mutations, levels of protein expression of oxidative stress, apoptosis, autophagy and mitophagy in breast cancer as well as the as...

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Main Author:	Omasanggar, Raevathi
Format:	Thesis
Language:	English
Published:	2021
Subjects:	Breast Neoplasms - pathology Oxidative Stress
Online Access:	http://psasir.upm.edu.my/id/eprint/93097/1/FPSK%20%28m%29%202021%207%20-IR.1.pdf
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id	my-upm-ir.93097
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spelling	my-upm-ir.930972022-10-18T04:56:07Z Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients 2021-01 Omasanggar, Raevathi Mitochondrial DNA (mtDNA) mutations, oxidative stress and resistance to cell deaths increase one’s risk for breast cancer. This study aims to identify the types of mtDNA mutations, levels of protein expression of oxidative stress, apoptosis, autophagy and mitophagy in breast cancer as well as the association between mtDNA mutations and the levels of protein expression. Female breast cancer patients (n=20) without neoadjuvant treatment were recruited with informed consents. Samples were 20 matched breast tumours with corresponding normal breast tissues. The entire mtDNA (16.6 kb) was sequenced using next-generation sequencing (NGS) and the levels of protein expressions were studied using tissue microarray and immunohistochemistry. A total of 18 of 20 patients had at least one somatic mtDNA mutation in their tumour samples. Overall, 65 somatic mutations were identified, with 30 novel mutations. The majority (59%) of the somatic mutations were in the coding region, whereas only (11%) of the mutations occurred in the D-loop. Notably, (15.4%) of somatic mutations in the protein-coding regions were potentially deleterious. A total of 753 germline mutations were identified and four of which were novel mutations. In comparison to somatic mutations, <1% of germline mutations are harmful. Immunohistochemistry study showed inconsistent expressions of MnSOD2, LC3B, BNIP3 and Parkin in breast cancer tissues. The expression of Beclin-1 was consistently positive and the expression of CC3 was consistently negative in all breast cancer cases. The differences in Beclin-1 expression between cancer and matched normal tissues were significant (p<0.001). Investigation of the relationship between somatic mtDNA mutations and protein expression levels of MnSOD2, CC3, LC3B, Beclin-1, BNIP3 and Parkin showed no significant differences. The findings of this study may enhance the current knowledge of mitochondrial-regulated cell mechanisms in breast cancer in Malaysia. Breast Neoplasms - pathology Oxidative Stress 2021-01 Thesis http://psasir.upm.edu.my/id/eprint/93097/ http://psasir.upm.edu.my/id/eprint/93097/1/FPSK%20%28m%29%202021%207%20-IR.1.pdf text en public masters Universiti Putra Malaysia Breast Neoplasms - pathology Oxidative Stress Maniam, Sandra
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
advisor	Maniam, Sandra
topic	Breast Neoplasms - pathology Oxidative Stress
spellingShingle	Breast Neoplasms - pathology Oxidative Stress Omasanggar, Raevathi Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients
description	Mitochondrial DNA (mtDNA) mutations, oxidative stress and resistance to cell deaths increase one’s risk for breast cancer. This study aims to identify the types of mtDNA mutations, levels of protein expression of oxidative stress, apoptosis, autophagy and mitophagy in breast cancer as well as the association between mtDNA mutations and the levels of protein expression. Female breast cancer patients (n=20) without neoadjuvant treatment were recruited with informed consents. Samples were 20 matched breast tumours with corresponding normal breast tissues. The entire mtDNA (16.6 kb) was sequenced using next-generation sequencing (NGS) and the levels of protein expressions were studied using tissue microarray and immunohistochemistry. A total of 18 of 20 patients had at least one somatic mtDNA mutation in their tumour samples. Overall, 65 somatic mutations were identified, with 30 novel mutations. The majority (59%) of the somatic mutations were in the coding region, whereas only (11%) of the mutations occurred in the D-loop. Notably, (15.4%) of somatic mutations in the protein-coding regions were potentially deleterious. A total of 753 germline mutations were identified and four of which were novel mutations. In comparison to somatic mutations, <1% of germline mutations are harmful. Immunohistochemistry study showed inconsistent expressions of MnSOD2, LC3B, BNIP3 and Parkin in breast cancer tissues. The expression of Beclin-1 was consistently positive and the expression of CC3 was consistently negative in all breast cancer cases. The differences in Beclin-1 expression between cancer and matched normal tissues were significant (p<0.001). Investigation of the relationship between somatic mtDNA mutations and protein expression levels of MnSOD2, CC3, LC3B, Beclin-1, BNIP3 and Parkin showed no significant differences. The findings of this study may enhance the current knowledge of mitochondrial-regulated cell mechanisms in breast cancer in Malaysia.
format	Thesis
qualification_level	Master's degree
author	Omasanggar, Raevathi
author_facet	Omasanggar, Raevathi
author_sort	Omasanggar, Raevathi
title	Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients
title_short	Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients
title_full	Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients
title_fullStr	Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients
title_full_unstemmed	Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients
title_sort	investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in malaysian breast cancer patients
granting_institution	Universiti Putra Malaysia
publishDate	2021
url	http://psasir.upm.edu.my/id/eprint/93097/1/FPSK%20%28m%29%202021%207%20-IR.1.pdf
_version_	1776100267881660416

Investigating interplay between mitochondrial dna mutations, oxidative stress and cell deaths in Malaysian breast cancer patients

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