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Title: An integrated molecular cytogenetic, genetic and pathological approach to facilitate the understanding of the biology of invasive ductal breast carcinoma
Author: Roylance, Rebecca Ruth
ISNI:       0000 0001 2419 838X
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2000
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The biological progression of breast cancer is uncertain. One hypothesis suggests that as invasive ductal breast tumours grow they dedifferentiate, i.e. they evolve from well-differentiated grade I tumours to poorly differentiated grade III tumours over time. The work presented here addresses the pathological hypothesis of dedifferentiation by taking a novel genetic approach. CGH was used to screen the entire genomes of 90 invasive ductal breast carcinomas stratified by grade (40 grade I and 50 grade III tumours). The different grades of breast tumour showed distinct quantitative and qualitative differences. Specifically, the genetic changes found could not support the dedifferentiation hypothesis for the majority of grade I breast carcinomas. These differences were investigated in a subsequent molecular genetic study that provides further evidence against dedifferentiation. The molecular cytogenetic findings have lead to several other lines of enquiry. First, the pattern of genetic changes seen in grade I tumours is very similar to that seen in lobular breast carcinomas, thus leading to the hypothesis that at the genetic level these morphologically distinct tumours may actually be very similar. In both these tumour types, the most frequent change, often occurring with only a few other genetic changes, is loss of 16q. The target gene on 16q known to be important in lobular breast tumorigenesis is E-cadherin (CDHl), therefore this candidate gene was tested in grade I ductal breast tumours. However, the findings suggest that in ductal breast carcinoma CDHl is not the target gene. Therefore, despite the apparent genetic similarity, lobular and grade I ductal breast tumours are genetically different. Second, a number of regions of amplification have been revealed in both grades of tumour; some of these are novel changes. Refined mapping of two amplicons has been performed, which will be discussed. Taken together, these findings integrate molecular cytogenetic, genetic and pathological approaches to provide new insights into the biology of breast tumour progression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available