| Titre : | Genetic association study and an in silico analysis of breast cancer |
| Auteurs : | Randa HALIMAOUI, Auteur ; Randa HALIMAOUI, Auteur ; BERBER,Naima, Directeur de thèse |
| Type de document : | texte imprimé |
| Editeur : | Dr. Moulay Tahar Université Saida, Faculté des Sciences Naturelles et de la Vie, 2023/2024 |
| Format : | 69 p / 29 cm |
| Accompagnement : | CD |
| Langues: | Anglais |
| Langues originales: | Anglais |
| Catégories : | |
| Mots-clés: | breast cancer ; BRCA1 ; mutations ; in silico analysis |
| Résumé : |
Breast cancer is a critical public health issue in Algeria, with increasing incidence and substantial challenges in diagnosis, treatment, and management. Breast cancer incidence in Algeria has increased significantly, with over 2.1 million women diagnosed in 2018. BRCA1, a pivotal gene in DNA repair and tumor suppression, is critically implicated in the predisposition to breast and ovarian cancers. In silico analysis has emerged as a powerful approach to understand the functional implications
of BRCA1 mutations, offering insights into their structural and mechanistic effects. This study leverages computational tools (I-Mutant 2.0), (SIFT), (Align-GVGD), (PolyPhen-2), (Project HOPE) software) to analyze the impact of various BRCA1 mutations on protein structure and function. By employing molecular modeling, sequence alignment, and predictive algorithms, we identify mutations that significantly disrupt BRCA1’s role in maintaining genomic stability. The analysis reveals key regions within the BRCA1 protein that are particularly susceptible to substituted alterations in two different in silico analysis. The (c. 135G>C) (p. Lys45Asn) mutation and (c. 122A>G) (p. His41Arg) mutation provide a framework for prioritizing mutations for experimental validation and clinical assessment. Additionally, we explore the potential of in silico findings to inform the development of targeted therapies. |
| Note de contenu : |
1 INTRODUCTION .............................................................................................. 1
2 DEFINITION AND EPIDEMIOLOGY ............................................................ 2 2.1 DEFINITION .................................................................................................. 2 2.2 EPIDEMIOLOGY ........................................................................................... 2 2.2.1 Patients disposition.................................................................................... 2 2.2.2 Demographics, clinical and disease characteristics .................................. 3 3 BREAST CANCER LOCALISATION ............................................................. 8 3.1 BREAST PARTS THAT CAN BE AFFECTED ........................................... 8 3.2 THE DIFFUSION OF BREAST CANCER ................................................... 9 4 BREAST CANCER TYPES ............................................................................ 10 4.1 SUBTYPES INCLUDE ................................................................................ 12 5 RISK FACTORS FOR BREAST CANCER ................................................... 13 5.1 RISK FACTORS THAT CAN’T BE CHANGED ....................................... 13 5.2 RISK FACTORS THAT CAN BE CHANGED ........................................... 14 6 CLINICAL ASPECTS ..................................................................................... 14 6.1 SYMPTOMES OF BREAST CANCER ....................................................... 14 6.1.1 Breast lump ............................................................................................. 15 6.1.2 Lump or sweeling in the armpit .............................................................. 15 6.1.3 Change in the size and shape .................................................................. 15 6.1.4 Skin changes ............................................................................................ 15 6.1.5 Fluid leaking from nipples ...................................................................... 16 6.1.6 Change in the position the nipple ............................................................ 16 6.1.7 Breast pain ............................................................................................... 16 6.2 TESTS FOR BREAST CANCER ................................................................. 16 6.2.1 GP test ..................................................................................................... 16 6.2.2 Breast cancer screening ........................................................................... 16 6.2.3 Mammogram ........................................................................................... 17 6.2.4 Breast ultrasound scan............................................................................. 17 6.2.5 Breast biopsy ........................................................................................... 18 6.2.6 Procedure after biopsy............................................................................. 21 6.2.7 Checking for cancer cells in the lymph nodes of the armpit .................. 21 6.2.8 Breast MRI (Magnetic Resonance Imaging) scan ................................. 226.2.9 CT (Computed Tomography) scan ......................................................... 22 6.2.10 Blood tests ............................................................................................. 23 6.2.11 Hormone receptors status testing .......................................................... 23 6.2.12 Bone scan .............................................................................................. 24 5 TREATMENTS ................................................................................................ 24 2 GENETIC ASPECTS ....................................................................................... 27 2.1 BRCA1 AND BRCA2 .................................................................................. 27 2.2 BRCA1 GENE .............................................................................................. 27 2.2.1 Structure and Function of BRCA1 Gene ................................................ 27 2.2.2 BRCA1 DNA repair associated .............................................................. 30 2.2.3 The Mutation of BRCA1 and Breast Cancer .......................................... 31 2.2.4 BRCA1 protein ....................................................................................... 32 3 BIOINFORMATICS ........................................................................................ 34 3.1 BIOINFORMATICS HISTORY................................................................... 36 3.2 BIOINFORMATIC TOOLS ......................................................................... 36 3.3 BIOINFORMATIC ANALYSIS .................................................................. 37 4 POPULATION OF THE STUDY.................................................................... 41 5 METHOD ......................................................................................................... 41 5.1 I-MUTANT 2.0 SOFTWARE....................................................................... 41 5.2 PROJECT HOPE SOFTWARE .................................................................... 42 5.3 ALIGN GVGD SOFTWARE ....................................................................... 43 5.4 POLYPHEN-2 SOFTWARE ........................................................................ 44 5.5 SIFT SOFTWARE ........................................................................................ 45 6 EXONIC MUTATION ANALYSIS OF (C.122A>G) (P. HIS41ARG) ......... 48 6.1 RESULT OBTAINED BY THE I-MUTANT 2.0 SOFTWARE ................. 48 6.2 RESULT OBTAINED BY PROJECT HOPE .............................................. 48 6.3 RESULT OBTAINED BY ALIGN GVGD .................................................. 50 6.4 RESULT OBTAINED BY POLYPHEN-2 SOFTWARE ............................ 51 6.5 RESULT OBTAINED BY SIFT SOFTWARE ............................................ 53 7 EXONIC MUTATION ANALYSIS OF (C.135G>C) (P. LYS45ASN) ......... 54 7.1 RESULT OBTAINED BY THE I-MUTANT 2.0 SOFTWARE ................. 54 7.2 RESULT OBTAINED BY PROJECT HOPE SOFTWARE ........................ 55 7.3 RESULT OBTAINED BY ALIGN GVGD SOFTWARE ........................... 57 7.4 RESULT OBTAINED BY POLYPHEN-2 SOFTWARE ............................ 587.5 RESULT OBTAINED BY SIFT SOFTWARE ............................................ 59 8 DISCUSSION .................................................................................................. 60 8.1 DISCUSSION OF (C.122A>G) (P. HIS41ARG) MUTATION RESULTS 60 8.2 DISCUSSION OF (C.135G>C) (P. LYS45ASN) MUTATION RESULTS 61 8.3 GENERAL DISCUSSION ............................................................................ 61 9 CONCLUSION ................................................................................................ 64 |
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