My NCBI
[Sign In] [Register]
Entrez PubMed Nucleotide Protein Genome Structure OMIM PMC Journals Books
Search PubMed Protein Nucleotide Structure Genome Books CancerChromosomes Conserved Domains 3D Domains Gene Genome Project GENSAT GEO Profiles GEO DataSets HomoloGene Journals MeSH NCBI Web Site NLM Catalog OMIM PMC PopSet PubChem BioAssay PubChem Compound PubChem Substance SNP Taxonomy UniGene UniSTS for
Limits Preview/Index History Clipboard Details
About Entrez
Text Version
Entrez PubMed
Overview
Help | FAQ
Tutorial
New/Noteworthy
E-Utilities
PubMed Services
Journals Database
MeSH Database
Single Citation Matcher
Batch Citation Matcher
Clinical Queries
LinkOut
My NCBI (Cubby)
Related Resources
Order Documents
NLM Catalog
NLM Gateway
TOXNET
Consumer Health
Clinical Alerts
ClinicalTrials.gov
PubMed Central Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut Related Articles Cited in Books CancerChrom Links Domain Links 3D Domain Links GEO DataSet Links Gene Links Genome Links Project Links GENSAT Links GEO Profile Links HomoloGene Links Nucleotide Links OMIM Links BioAssay Links Compound Links Compound via MeSH Substance Links Substance via MeSH PMC Links Cited in PMC PopSet Links Protein Links SNP Links Structure Links UniSTS Links Show: 5 10 20 50 100 200 500 Sort Author Journal Pub Date Text File Clipboard E-mail Order
All: 1
1: Maturitas. 2004 Sep 24;49(1):34-43. Related Articles, Links
Oncogenic pathways in hereditary and sporadic breast cancer.
Kenemans P, Verstraeten RA, Verheijen RH.
Department of Obstetrics and Gynaecology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Kenemans@vumc.nl
Cancer is a genetic disease. Breast cancer tumorigenesis can be described as a multi-step process in which each step is thought to correlate with one or more distinct mutations in major regulatory genes. The question addressed is how far a multi-step progression model for sporadic breast cancer would differ from that for hereditary breast cancer. Hereditary breast cancer is characterized by an inherited susceptibility to breast cancer on basis of an identified germline mutation in one allele of a high penetrance susceptibility gene (such as BRCA1, BRCA2, CHEK 2, TP53 or PTEN). Inactivation of the second allele of these tumour suppressor genes would be an early event in this oncogenic pathway (Knudson's "two-hit" model). Sporadic breast cancers result from a serial stepwise accumulation of acquired and uncorrected mutations in somatic genes, without any germline mutation playing a role. Mutational activation of oncogenes, often coupled with non-mutational inactivation of tumour suppressor genes, is probably an early event in sporadic tumours, followed by more, independent mutations in at least four or five other genes, the chronological order of which is likely less important. Oncogenes that have been reported to play an early role in sporadic breast cancer are MYC, CCND1 (Cyclin D1) and ERBB2 (HER2/neu). In sporadic breast cancer, mutational inactivation of BRCA1/2 is rare, as inactivation requires both gene copies to be mutated or totally deleted. However, non-mutational functional suppression could result from various mechanisms, such as hypermethylation of the BRCA1 promoter or binding of BRCA2 by EMSY. In sporadic breast tumorigenesis, at least three different pathway-specific mechanisms of tumour progression are recognizable, with breast carcinogenesis being different in ductal versus lobular carcinoma, and in well differentiated versus poorly differentiated ductal cancers. Thus, different breast cancer pathways emerge early in the process of carcinogenesis, ultimately leading to clinically different tumour types. As mutations acquired early during tumorigenesis will be present in all later stages, large-scale gene expression profiling using DNA microarray analysis techniques can help to classify breast cancers into clinically relevant subtypes.
Publication Types:
Review
Review, Tutorial
PMID: 15351094 [PubMed - indexed for MEDLINE]
-- ------------------------------------------------------------------------------
Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut Related Articles Cited in Books CancerChrom Links Domain Links 3D Domain Links GEO DataSet Links Gene Links Genome Links Project Links GENSAT Links GEO Profile Links HomoloGene Links Nucleotide Links OMIM Links BioAssay Links Compound Links Compound via MeSH Substance Links Substance via MeSH PMC Links Cited in PMC PopSet Links Protein Links SNP Links Structure Links UniSTS Links Show: 5 10 20 50 100 200 500 Sort Author Journal Pub Date Text File Clipboard E-mail Order
Write to the Help Desk
NCBI | NLM | NIH
Department of Health & Human Services
Privacy Statement | Freedom of Information Act | Disclaimer
Feb 10 2005 12:03:04