Identification of a Preneoplastic Gene Expression Profile in Tubal Epithelium of BRCA1 Mutation Carriers
| Autor: | Barbara M. Norquist, Rochelle L. Garcia, Barbara A. Goff, Joshua Z. Press, Piri Welcsh, C. Pennil, Elizabeth M. Swisher, Kaitlyn Wurz, Ming K. Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty endocrine system diseases Genes BRCA2 Genes BRCA1 Fluorescent Antibody Technique Biology Carcinoma Ovarian Epithelial lcsh:RC254-282 Epithelium Metastasis 03 medical and health sciences 0302 clinical medicine Fallopian Tube Neoplasm medicine Fallopian Tube Neoplasms Humans Genes Tumor Suppressor Genetic Predisposition to Disease Neoplasms Glandular and Epithelial skin and connective tissue diseases Cyclin-Dependent Kinase Inhibitor p57 Fallopian Tubes 030304 developmental biology Laser capture microdissection Ovarian Neoplasms 0303 health sciences Frozen section procedure Extracellular Matrix Proteins Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gene expression profiling medicine.anatomical_structure Ki-67 Antigen E2F3 Transcription Factor 030220 oncology & carcinogenesis Mutation Immunohistochemistry Female Precancerous Conditions Fallopian tube Research Article |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 12, Iss 12, Pp 993-1002 (2010) |
| ISSN: | 1522-8002 1476-5586 |
| Popis: | Microinvasive carcinomas and high-grade intraepithelial neoplasms are commonly discovered within the fallopian tube of BRCA1 mutation carriers at the time of risk-reducing salpingo-oophorectomy, suggesting that many BRCA1-mutated ovarian carcinomas originate in tubal epithelium. We hypothesized that changes in gene expression profiles within the histologically normal fallopian tube epithelium of BRCA1 mutation carriers would overlap with the expression profiles in BRCA1-mutated ovarian carcinomas and represent a BRCA1 preneoplastic signature. Laser capture microdissection of frozen sections was used to isolate neoplastic cells or histologically normal fallopian tube epithelium, and expression profiles were generated on Affymetrix U133 Plus 2.0 gene expression arrays. Normal-risk controls were 11 women wild type for BRCA1 and BRCA2 (WT-FT). WT-FT were compared with histologically normal fallopian tube epithelium from seven women with deleterious BRCA1 mutations who had foci of at least intraepithelial neoplasm within their fallopian tube (B1-FTocc). WT-FT samples were also compared with 12 BRCA1 ovarian carcinomas (B1-CA). The comparison of WT-FT versus B1-FTocc resulted in 152 differentially expressed probe sets, and the comparison of WT-FT versus B1-CA resulted in 4079 differentially expressed probe sets. The BRCA1 preneoplastic signature was composed of the overlap between these two lists, which included 41 concordant probe sets. Genes in the BRCA1 preneoplastic signature included several known tumor suppressor genes such as CDKN1C and EFEMP1 and several thought to be important in invasion and metastasis such as E2F3. The expression of a subset of genes was validated with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. |
| Databáze: | OpenAIRE |
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