Functional and Molecular Characterization of BRCA1 and BRCA2 Associated Breast Cancer

Abstract

This doctoral dissertation is based on five appended papers primarily concerned with three main topics, namely: the functional characterization of specific and clinically relevant perturbations found in BRCA1 ? one of the major breast cancer susceptibility genes; the use of microarray technologies for molecular characterization of hereditary breast tumor samples from a genomic perspective; and finally, the development of software to address some of the logistical problems of data analysis and management that arise when utilizing microarrays. Results obtained from the work presented herein demonstrate the following: that transcription az says can aid in the characterization of C-terminal missense mutations but that it may not be possible to unambiguously characterize variants with a yeast-based assay alone; that a naturally occurring C-terminal germline mutation in BRCA1 encodes a protein with apparent temperature-dependant functional properties; that open-source software can provide comprehensive solutions to meet data management needs of microarray experimenters; that BRCA1 and BRCA2 associated breast tumors exhibit markedly different copy number aberrations when compared to each other as well as to sporadic tumors; and that gene expression profiling in BRCA1 and BRCA2 associated breast tumors reveals specific gene expression patterns.

• author: Vallon-Christersson, Johan
• supervisor: Åke Borg; Markus Ringnér
• opponent: Professor Quackenbush, John, The Institute for Genomic Research, Rockville, Maryland, USA
• organization: Breastcancer-genetics
• publishing date: 2005
• type: Thesis
• publication status: published
• subject: Cancer and Oncology
• keywords: onkologi, cancer, Cytologi, cancerology, Cytology, BioArray Software Environment, BASE, Software, Open-source, Copy number, Gene expression, Microarray, BRCA2, BRCA1, Breast cancer, Hereditary cancer, oncology
• pages: 146 pages
• defense location: Segerfalk lecture hall, Wallenberg Neuroscience Center, Lund.
• defense date: 2005-03-30 13:00:00
• ISBN: 91-85439-14-2
• language: English
• LU publication?: yes
• additional info: J Vallon-Christersson, C Cayanan, K Haraldsson, N Loman, JT Bergthorsson, K Brodum-Nielsen, AM Gerdes, P Moller, U Kristoffersson, H Olsson, Å Borg and AN Monteiro. 2001. Functional analysis of BRCA1 C-terminal missense mutations identified in breast and ovarian cancer families. Hum Mol Genet, vol 10 pp 353-60.; T Worley, J Vallon-Christersson, B Billack, Å Borg and AN Monteiro. 2002. A naturally occurring allele of BRCA1 coding for a temperature-sensitive mutant protein. Cancer Biol Ther, vol 1 pp 497-501.; LH Saal, C Troein, J Vallon-Christersson, S Gruvberger, Å Borg and C Peterson. 2002. BioArray Software Environment (BASE): a platform for comprehensive management and analysis of microarray data. Genome Biol, vol 3 pp SOFTWARE0003.; G Jönsson, TL Naylor, J Vallon-Christersson, J Staaf, J Huang, MR Ward, JD Greshock, L Luts, N Rahman, M Stratton, H Olsson, M Ringnér, Å Borg and BL Weber. . Distinct genomic profiles in hereditary breast tumors indentified by array-based comparative genomic hybridization. (submitted); J Vallon-Christersson, G Jönsson, M Ringnér, A Arason, R Fagerholm, C Hegardt, K Holm, E Niméus, C Persson, BA Agnarsson, OT Johannsson, L Luts, H Olsson, H Nevanlinna, RB Barkardottir and Å Borg. . Gene expression profiling of BRCA1 and BRCA2 associated and sporadic breast tumors. (manuscript)
• id: 7a590914-d2ea-40ae-8e87-6e4617040341 (old id 544465)
• date added to LUP: 2016-04-01 16:29:10
• date last changed: 2022-05-04 08:05:15