Project description:Tumor associated miRNAs in hereditary breast cancer. In this study we investigated the role of miRNAs in hereditary breast tumors comparing with normal breast tissue. Global miRNA expression profiling was performed on 22 hereditary breast tumors and 15 non-tumoral breast tissues. We identified 19 miRNAs differentially expressed, most of them down-regulated in tumors. An important proportion of deregulated miRNAs in hereditary tumors were previously identified commonly deregulated in sporadic breast tumors. Our results identify miRNAs associated to hereditary breast cancer, as well as miRNAs commonly miss-expressed in hereditary and sporadic tumors, suggesting common underlying mechanisms of tumor progression. In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling. Single color experiments in a pairwise comparison design.
Project description:The objective of the study was to characterize hereditary breast tumors based on their miRNA expression profiles. To this end, we performed global miRNA expression analysis of more than 800 human miRNA genes in a large series of 80 FFPE breast tissue samples. The series included 66 hereditary breast primary tumors from 13 BRCA1 mutation carriers, 10 BRCA2 mutation carriers and 43 non-BRCA12 tumors denominated hereafter as BRCAX tumors. In addition we have analyzed 10 sporadic breast carcinomas and 4 normal breast tissues obtained after breast reduction surgery from healthy donors with no family history of breast cancer. To avoid contamination with normal breast tissue, tumoral area on FFPE blocks was marked by a pathologist and macrodissected for subsequent total RNA extraction. Microarray expression profiling was performed using miRCURY LNATM microRNA Array v.11 (Exiqon A/S, Denmark), in a single color experiments in a pairwise comparison experimantal design.
Project description:The objective of the study was to characterize hereditary breast tumors based on their miRNA expression profiles. To this end, we performed global miRNA expression analysis of more than 800 human miRNA genes in a large series of 80 FFPE breast tissue samples. The series included 66 hereditary breast primary tumors from 13 BRCA1 mutation carriers, 10 BRCA2 mutation carriers and 43 non-BRCA12 tumors denominated hereafter as BRCAX tumors. In addition we have analyzed 10 sporadic breast carcinomas and 4 normal breast tissues obtained after breast reduction surgery from healthy donors with no family history of breast cancer. To avoid contamination with normal breast tissue, tumoral area on FFPE blocks was marked by a pathologist and macrodissected for subsequent total RNA extraction.
Project description:Tumor associated miRNAs in hereditary breast cancer. In this study we investigated the role of miRNAs in hereditary breast tumors comparing with normal breast tissue. Global miRNA expression profiling was performed on 22 hereditary breast tumors and 15 non-tumoral breast tissues. We identified 19 miRNAs differentially expressed, most of them down-regulated in tumors. An important proportion of deregulated miRNAs in hereditary tumors were previously identified commonly deregulated in sporadic breast tumors. Our results identify miRNAs associated to hereditary breast cancer, as well as miRNAs commonly miss-expressed in hereditary and sporadic tumors, suggesting common underlying mechanisms of tumor progression. In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling.
Project description: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. 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
Project description:Papillary renal cell carcinoma type 2 (PRCC2) is known to be very aggressive type of tumor without effictive therapy. Hereditary form of PRCC2 is caused by Fumarate Hydratase (FH) gene mutation that accompanied Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) disorder. In sporadic form of PRCC2 the mutation of FH gene has not been reported. Both forms of tumors have the similar histopathological characteristics with poor survival prognosis. In this study, we profiled the gene expression of renal tumors and normal tissue from PRCC2 (hereditary and sporadic) patients in order to better understand commonalities and differences in the transcriptional landscape of PRCC2. Microarray gene expression profiling was performed on eight normal kidney tissue samples, five hereditary PRCC2 tumor tissue samples and 19 sporadic PRCC2 tumor tissue samples. Hereditary PRCC2 (HPRCC2) patients were confirmed by DNA sequencing of the FH gene.