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| Status |
Public on Sep 05, 2013 |
| Title |
BRCA1-related gene signature in breast cancer: the role of ER status and molecular type |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
We have analyzed, using DNA microarrays, putative differences in gene-expression level between hereditary BRCA1 mutation-linked and sporadic breast cancer. Our results show that a previously reported marked difference between BRCA1-mutation linked and sporadic breast cancer was probably due to uneven stratification of samples with different ER status and basal-like versus luminal-like subtype. We observed that apparent difference between BRCA1-linked and other types of breast cancer found in univariate analysis was diminished when data were corrected for ER status and molecular subtype in multivariate analyses. In fact, the difference in gene expression pattern of BRCA1-mutated and sporadic cancer is very discrete. These conclusions were supported by the results of Q-PCR validation. We also found that BRCA1 gene inactivation due to promoter hypermethylation had similar effect on general gene expression profile as mutation-induced protein truncation. This suggests that in the molecular studies of hereditary breast cancer, BRCA1 gene methylation should be recognized and considered together with gene mutation.
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| Overall design |
We analyzed 35 breast cancer specimens. Surgical samples obtained during mastectomy were flash-frozen in liquid nitrogen and stored at -80°C. Only samples from patients without neoadjuvant chemotherapy were used in this study as chemotherapy may seriously affect gene expression profile. All tissue samples were collected at the Pomeranian Medical University in Szczecin. Seventeen tumor samples were collected from patients with hereditary breast cancer: 12 were derived from tumors affecting women with hereditary BRCA1 mutation, the only one from a woman with BRCA2 mutation, while another eight cases had familial history of breast/ovarian cancer, but were negative for the BRCA1/2 mutations (so called BRCAx cases). Proportion of BRCA1 and BRCA2 mutated tumors was typical for the Polish population. Ten samples were derived from patients with apparently sporadic disease (no familial history of cancer) while 4 patients had a history of familial cancer aggregation (FCA) but without prevalence of breast/ovarian cancers. Thus, these samples were merged with sporadic samples in most of the analyses. All BRCA1 mutation-linked tumors in our study were negative for estrogen receptor (by immunohistochemistry, standard procedures for ER, PGR and HER2 staining were applied), while the only BRCA2-mutated tumor was ER-positive. There were 26 ductal and 5 medullary carcinomas within the study group, which is consistent with the distribution of histopathological types in BRCA1 mutation carriers. Patients were diagnosed at stage T1-2, N0-1 and M0. Caution: this submission contains the data from 6 microarrays done on the normal/pathologically unchanged breast tissue from breast cancer patiets. The data from normal tissues was not analyzed in the paper BRCA1-related gene signature in breast cancer is strongly influenced by ER status and molecular type by Lisowska et al., 2011, Front Biosci (Elite Ed). 2011 Jan 1;3:125-36
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| Contributor(s) |
Lisowska K |
| Citation(s) |
21196292 |
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| Submission date |
Sep 04, 2013 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Katarzyna Marta Lisowska |
| E-mail(s) |
klisowska@io.gliwice.pl
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| Organization name |
MSC Memorial Cancer Center and Institute of Oncology, Gliwice Branch
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| Department |
Center for Translational Research and Molecular Biology of Cancer
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| Street address |
ul. Wybrzeże Armii Krajowej 15
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| City |
Gliwice |
| ZIP/Postal code |
44-101 |
| Country |
Poland |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (41)
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| GSM1223656 |
hereditary, BRCA1-mutated, sample 09B |
| GSM1223657 |
hereditary, BRCA1-mutated, sample 11 |
| GSM1223658 |
hereditary, BRCA1-mutated, sample 12 |
| GSM1223659 |
hereditary, BRCA1-mutated, sample 14 |
| GSM1223660 |
hereditary, BRCA1-mutated, sample 17 |
| GSM1223661 |
hereditary, BRCA1-mutated, sample 21 |
| GSM1223662 |
hereditary, BRCA1-mutated, sample 26 |
| GSM1223663 |
hereditary, BRCA1-mutated, sample 28 |
| GSM1223664 |
hereditary, BRCA1-mutated, sample 33 |
| GSM1223665 |
hereditary, BRCA2-mutated, sample 10 |
| GSM1223666 |
hereditary, BRCAx, sample 04 |
| GSM1223667 |
hereditary, BRCAx, sample 19 |
| GSM1223668 |
hereditary, BRCAx, sample 24 |
| GSM1223669 |
hereditary, BRCAx, sample 32 |
| GSM1223670 |
hereditary, BRCAx, sample 35 |
| GSM1223671 |
hereditary, BRCAx, sample 08 |
| GSM1223672 |
hereditary, BRCAx, sample 36 |
| GSM1223673 |
hereditary, BRCAx, sample 37 |
| GSM1223674 |
sporadic, sample 06 |
| GSM1223675 |
sporadic, sample 07 |
| GSM1223676 |
sporadic, sample 13 |
| GSM1223677 |
sporadic, sample 20 |
| GSM1223678 |
sporadic, sample 22 |
| GSM1223679 |
sporadic, sample 27 |
| GSM1223680 |
sporadic, sample 29 |
| GSM1223681 |
sporadic, sample 31 |
| GSM1223682 |
sporadic, sample 34 |
| GSM1223683 |
sporadic, sample 05 |
| GSM1223684 |
sporadic /FCA (familial cancer aggregation), sample 15 |
| GSM1223685 |
sporadic /FCA (familial cancer aggregation), sample 18 |
| GSM1223686 |
sporadic /FCA (familial cancer aggregation), sample 25 |
| GSM1223687 |
sporadic /FCA (familial cancer aggregation), sample 30 |
| GSM1223688 |
normal breast, sample n02 |
| GSM1223689 |
normal breast, sample n03 |
| GSM1223690 |
normal breast, sample 07 |
| GSM1223691 |
normal breast, sample n11 |
| GSM1223692 |
normal breast, sample n12 |
| GSM1223693 |
normal breast, sample n21 |
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| Relations |
| BioProject |
PRJNA217957 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50567_RAW.tar |
208.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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