Characterization of hereditary cancer syndromes
department or school: Medicine, Faculty of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Schrader, Kasmintan Alexandra
issued: 2013-05-28T09:10:50Z
issued: 2013
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Hereditary cancer syndromes predispose to early-onset or multiple cancers in a person or family, follow Mendelian inheritance patterns and demonstrate stereotyped patterns of tumor development. Genotype-phenotype correlations direct clinical genetic testing and provide guidance for hereditary cancer management. This thesis began by examining the association of lobular breast cancer with germline mutations in CDH1, the gene encoding the epithelial cell-cell adhesion molecule E-cadherin and tested whether CDH1 represented a high-frequency breast cancer susceptibility gene, apart from its association with hereditary diffuse gastric cancer. In addition it examined other genotype-phenotype correlations including the association between granular cell tumors and a multiple congenital anomaly syndrome, the specific correlation between a recurrent somatic mutation in a transcription factor and adult-type granulosa cell tumors and the strong association of germline BRCA1 and BRCA2 mutations with high-grade serous epithelial ovarian cancer. These candidate gene analyses were performed using low-throughput molecular technologies. With the advent of cheaper DNA-sequencing capabilities, the application of these new technologies to novel Mendelian disease gene discovery and hereditary cancer management became the subsequent focus of the thesis. Objectives: To determine the frequency of germline CDH1 mutations in women with lobular breast cancer unselected for familial gastric cancer; to define the associations between several alternative genotype-phenotype correlations; and, to apply next-generation sequencing to determine the basis of a Mendelian disorder, in order to determine its utility as a potential familial cancer gene discovery and clinical tool. Selected Methods: Single amplicon mutation screening and sequence analysis of a large cohort of women with early-onset or familial lobular breast cancer. Next-generation sequencing analysis of a family with multiple individuals co…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/44512
note: i CHARACTERIZATION OF HEREDITARY CANCER SYNDROMES by Kasmintan Alexandra Schrader M.B.B.S., The University of British Columbia, 2013 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate Studies (Pathology and Laboratory Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) May 2013 © Kasmintan Alexandra Schrader, 2013 ii Abstract Hereditary cancer syndromes predispose to early-onset or multiple cancers in a person or family, follow Mendelian inheritance patterns and demonstrate stereotyped patterns of tumor development. Genotype-phenotype correlations direct clinical genetic testing and provide guidance for hereditary cancer management. This thesis began by examining the association of lobular breast cancer with germline mutations in CDH1, the gene encoding the epithelial cell-cell adhesion molecule E-cadherin and tested whether CDH1 represented a high-frequency breast cancer susceptibility gene, apart from its association with hereditary diffuse gastric cancer. In addition it examined other genotype-phenotype correlations including the association between granular cell tumors and a multiple congenital anomaly syndrome, the specific correlation between a recurrent somatic mutation in a transcription factor and adult-type granulosa cell tumors and the strong association of germline BRCA1 and BRCA2 mutations with high-grade serous epithelial ovarian cancer. These candidate gene analyses were performed using low- throughput molecular technologies. With the advent of cheaper DNA-sequencing capabilities, the application of these new technologies to novel Mendelian disease gene discovery and hereditary cancer management became the subsequent focus of the thesis. Objectives: To determine the frequency of germline CDH1 mutations in women with lobular breast cancer unselected for familial gastric cancer; to define the associations between several alternative genotype-phenotype correlations; and, to…
has type: Thesis/Dissertation
date issued: 2013-11
is shown at: 10.14288/1.0073862
language: eng
degree discipline: Pathology and Laboratory Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/44512