Áhrif BRCA2-kímlínustökkbreytingar á krabbameinsmyndun og sjúkdómsframvindu

Verkefnislok - fréttatilkynning verkefnisstjóra


The objectives of this project were to carry out detailed molecular profiling and phenotypic characterization of BRCA2 and BRCA1 related tumours, in relation to non-carrier tumours, and to define subgroups with respect to genetic networks linked to tumour progression.

Heiti verkefnis: Áhrif BRCA2-kímlínustökkbreytingar á krabbameinsmyndun og sjúkdómsframvindu
Verkefnisstjóri:  Jórunn Erla Eyfjörð, HÍ

Tegund styrks: Verkefnisstyrkur
Styrkár: 2011-2013
Styrkfjárhæð: 19,5 millj. kr. alls
Tilvísunarnúmer Rannís: 110449

Different microarray profiling methods were used to define tumour characteristics and subgroups.  Identified subgroups were then analysed with respect to clinical data. Network analyses were carried out to study gene interactions and their clinical relevance in defined subgroups.  Direct sequencing was carried out on a subset of the tumours and normal DNA from the same individuals.  All tumours that were studied from BRCA1 and BRCA2 mutation carriers were characterized by DNA deletions as was demonstrated using copy number microarrays (aCGH), but the deletions involved different chromosomal regions. BRCA2 tumours can in addition be divided into different subgroups of Luminal versus Basal-like/TNP type. These subgroups differ with respect to their path of tumorigenesis and progression. Loss of the normal BRCA2 allele was shown not to be necessary for initiation of carcinogenesis in the BRCA2 carriers, contrary to previously accepted view. However, loss of the normal BRCA2 allele was shown to be significantly associated with aggressive tumour progression in the Luminal type BRCA2 breast tumours.  Molecular profiling, using copy number (aCGH) or tissue microarrays (TMAs), as well as methylation analyses, also showed that a larger group of breast cancers than the BRCA mutation carriers alone were BRCA-like in character. Whole genome sequencing confirmed this finding.  Several ongoing studies are presently following-up data on potential prognostic markers identified in these studies. These studies have so far contributed, to a varying degree, to 21 scientific publication from 2011-2014 (see list under section II) and to completion of one PhD and one MSc degree. Results have also been presented at conferences and as part of invited lectures, both locally and abroad.

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