BRCA1 and BRCA2 and the genetics of breast and ovarian cancer.
P. Welcsh, and M. King. Hum Mol Genet, 10 (7):
705-713(April 2001)
Abstract
Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose
individuals to breast and ovarian cancers. Progress in determining
the function of BRCA1 and BRCA2 suggests that they are involved in
two fundamental cellular processes: DNA damage repair and transcriptional
regulation. We evaluate current knowledge of BRCA1 and BRCA2 functions
to explain why mutations in BRCA1 and BRCA2 lead specifically to
breast and ovarian cancer. The BRCA1 and BRCA2 genes contain unusually
high densities of repetitive elements. These features of the BRCAs
genomic regions contribute to chromosomal instability of these genes.
We propose that somatic alterations of BRCA1 and BRCA2 are common
and driven by rearrangements between repetitive elements. Inherited
and somatic mutations occur in BRCA1 and BRCA2; virtually all somatic
mutations are the result of large genomic rearrangements. What are
the consequences of such large somatic mutations of BRCA1 and BRCA2
in women with or without inherited mutations? The breast and ovary
are estrogen-responsive tissues. Beginning in puberty, the breast
epithelium proliferates rapidly in response to fluctuating levels
of estrogen. We present a genetic model outlining how BRCA-deficient
cells may gain uncontrolled proliferation leading to tumor formation.
Central to this model of BRCA-mediated tumorigenesis are estrogen-mediated
proliferation of breast and ovarian epithelium and the distinctive
genomic context of the BRCA genes.
%0 Journal Article
%1 Welcsh2001
%A Welcsh, P. L.
%A King, M. C.
%D 2001
%J Hum Mol Genet
%K BRCA2_Protein Breast_Neoplasms,_genetics Cell_Division Chromosomes,_ultrastructure Estrogens,_metabolism Female Gene_Deletion Genes,_BRCA1,_genetics Genetic_Predisposition_to_Disease Humans Models,_Biological Mutation Neoplasm_Proteins,_genetics Ovarian_Neoplasms,_genetics Repetitive_Sequences,_Nucleic_Acid Transcription_Factors,_genetics
%N 7
%P 705-713
%T BRCA1 and BRCA2 and the genetics of breast and ovarian cancer.
%V 10
%X Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose
individuals to breast and ovarian cancers. Progress in determining
the function of BRCA1 and BRCA2 suggests that they are involved in
two fundamental cellular processes: DNA damage repair and transcriptional
regulation. We evaluate current knowledge of BRCA1 and BRCA2 functions
to explain why mutations in BRCA1 and BRCA2 lead specifically to
breast and ovarian cancer. The BRCA1 and BRCA2 genes contain unusually
high densities of repetitive elements. These features of the BRCAs
genomic regions contribute to chromosomal instability of these genes.
We propose that somatic alterations of BRCA1 and BRCA2 are common
and driven by rearrangements between repetitive elements. Inherited
and somatic mutations occur in BRCA1 and BRCA2; virtually all somatic
mutations are the result of large genomic rearrangements. What are
the consequences of such large somatic mutations of BRCA1 and BRCA2
in women with or without inherited mutations? The breast and ovary
are estrogen-responsive tissues. Beginning in puberty, the breast
epithelium proliferates rapidly in response to fluctuating levels
of estrogen. We present a genetic model outlining how BRCA-deficient
cells may gain uncontrolled proliferation leading to tumor formation.
Central to this model of BRCA-mediated tumorigenesis are estrogen-mediated
proliferation of breast and ovarian epithelium and the distinctive
genomic context of the BRCA genes.
@article{Welcsh2001,
abstract = {Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose
individuals to breast and ovarian cancers. Progress in determining
the function of BRCA1 and BRCA2 suggests that they are involved in
two fundamental cellular processes: DNA damage repair and transcriptional
regulation. We evaluate current knowledge of BRCA1 and BRCA2 functions
to explain why mutations in BRCA1 and BRCA2 lead specifically to
breast and ovarian cancer. The BRCA1 and BRCA2 genes contain unusually
high densities of repetitive elements. These features of the BRCAs
genomic regions contribute to chromosomal instability of these genes.
We propose that somatic alterations of BRCA1 and BRCA2 are common
and driven by rearrangements between repetitive elements. Inherited
and somatic mutations occur in BRCA1 and BRCA2; virtually all somatic
mutations are the result of large genomic rearrangements. What are
the consequences of such large somatic mutations of BRCA1 and BRCA2
in women with or without inherited mutations? The breast and ovary
are estrogen-responsive tissues. Beginning in puberty, the breast
epithelium proliferates rapidly in response to fluctuating levels
of estrogen. We present a genetic model outlining how BRCA-deficient
cells may gain uncontrolled proliferation leading to tumor formation.
Central to this model of BRCA-mediated tumorigenesis are estrogen-mediated
proliferation of breast and ovarian epithelium and the distinctive
genomic context of the BRCA genes.},
added-at = {2010-01-26T20:35:53.000+0100},
author = {Welcsh, P. L. and King, M. C.},
biburl = {https://www.bibsonomy.org/bibtex/2d95e2424abf7f355c65afb40f9397399/denilw},
institution = {Departments of Medicine and Genetics, Box 357720, University of Washington,
Seattle, WA 98195-7720, USA. piri@u.washington.edu},
interhash = {8aa4f9ca1cd99ee8755d30d53026ac6e},
intrahash = {d95e2424abf7f355c65afb40f9397399},
journal = {Hum Mol Genet},
keywords = {BRCA2_Protein Breast_Neoplasms,_genetics Cell_Division Chromosomes,_ultrastructure Estrogens,_metabolism Female Gene_Deletion Genes,_BRCA1,_genetics Genetic_Predisposition_to_Disease Humans Models,_Biological Mutation Neoplasm_Proteins,_genetics Ovarian_Neoplasms,_genetics Repetitive_Sequences,_Nucleic_Acid Transcription_Factors,_genetics},
month = Apr,
number = 7,
owner = {denilw},
pages = {705-713},
pmid = {11257103},
timestamp = {2010-01-26T20:36:05.000+0100},
title = {BRCA1 and BRCA2 and the genetics of breast and ovarian cancer.},
volume = 10,
year = 2001
}