Publications of Meriem BOUKERROUCHA
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See detailTranscriptome wide analysis of natural antisense transcripts shows potential role in breast cancer
Wenric, Stéphane ULiege; El Guendi, Sonia ULiege; CABERG, Jean-Hubert ULiege et al

Poster (2017, May)

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer ... [more ▼]

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer. Among them, natural antisense transcripts (NAT) are RNA sequences which are complementary and overlapping to those of protein-coding transcripts (PCT). NATs were punctually described as regulating gene expression, and are expected to act more frequently in cis than other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired healthy tissues were analyzed by strand-specific RNA sequencing. To highlight the potential role of NATs in gene regulations occurring in breast cancer, three different gene extraction methods were used: differential expression analysis of NATs between tumor and healthy tissues, differential correlation analysis of paired NAT/PCT between tumor and healthy tissues, and NAT/PCT read count ratio variation between tumor and healthy tissues. Each of these methods yielded lists of NAT/PCT pairs that were demonstrated to be enriched in survival-associated genes on an independent cohort (TCGA). This work allows to highlight NAT lists that display a strong potential to affect the expression of genes involved in the breast cancer pathology. [less ▲]

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See detailTranscriptome-wide analysis of natural antisense transcripts shows their potential role in breast cancer.
Wenric, Stéphane ULiege; ElGuendi, Sonia; CABERG, Jean-Hubert ULiege et al

in Scientific Reports (2017), 7(1), 17452

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense ... [more ▼]

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense transcripts (ncNAT) are RNA sequences that are complementary and overlapping to those of either protein-coding (PCT) or non-coding transcripts. Several ncNATs were described as regulating protein coding gene expression on the same loci, and they are expected to act more frequently in cis compared to other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired adjacent non-malignant tissues were analyzed by strand-specific RNA sequencing. To highlight ncNATs potentially playing a role in protein coding gene regulations that occur in breast cancer, three different data analysis methods were used: differential expression analysis of ncNATs between tumor and non-malignant tissues, differential correlation analysis of paired ncNAT/PCT between tumor and non-malignant tissues, and ncNAT/PCT read count ratio variation between tumor and non-malignant tissues. Each of these methods yielded lists of ncNAT/PCT pairs that were enriched in survival-associated genes. This work highlights ncNAT lists that display potential to affect the expression of protein-coding genes involved in breast cancer pathology. [less ▲]

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See detailCirculating microRNA-based screening tool for breast cancer
Freres, Pierre ULiege; Wenric, Stéphane ULiege; BOUKERROUCHA, Meriem ULiege et al

in Oncotarget (2015)

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative ... [more ▼]

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative screening procedure to mammography for breast cancer diagnosis. A plasma miRNA profile was determined by RT-qPCR in a cohort of 378 women. A diagnostic model was designed based on the expression of 8 miRNAs measured first in a profiling cohort composed of 41 primary breast cancers and 45 controls, and further validated in diverse cohorts composed of 108 primary breast cancers, 88 controls, 35 breast cancers in remission, 31 metastatic breast cancers and 30 gynecologic tumors. A receiver operating characteristic curve derived from the 8-miRNA random forest based diagnostic tool exhibited an area under the curve of 0.81. The accuracy of the diagnostic tool remained unchanged considering age and tumor stage. The miRNA signature correctly identified patients with metastatic breast cancer. The use of the classification model on cohorts of patients with breast cancers in remission and with gynecologic cancers yielded prediction distributions similar to that of the control group. Using a multivariate supervised learning method and a set of 8 circulating miRNAs, we designed an accurate, minimally invasive screening tool for breast cancer. [less ▲]

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See detailBRCA1 germline mutation and glioblastoma development: report of cases
Boukerroucha, Meriem ULiege; Josse, Claire ULiege; SEGERS, Karin ULiege et al

in BMC Cancer (2015), 15

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma ... [more ▼]

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma malignancy has ever been highlighted. Here we report two cases of BRCA1 mutated patients who developed a glioblastoma (GBM). Cases presentation Two patients diagnosed with triple negative breast cancer (TNBC) were screened for BRCA1 germline mutation. They both carried a pathogenic mutation introducing a premature STOP codon in the exon 11 of the BRCA1 gene. Few years later, both patients developed a glioblastoma and a second breast cancer. In an attempt to clarify the role played by a mutated BRCA1 allele in the GBM development, we investigated the BRCA1 mRNA and protein expression in breast and glioblastoma tumours for both patients. The promoter methylation status of this gene was also tested by methylation specific PCR as BRCA1 expression is also known to be lost by this mechanism in some sporadic breast cancers. Conclusion Our data show that BRCA1 expression is maintained in glioblastoma at the protein and the mRNA levels, suggesting that loss of heterozygosity (LOH) did not occur in these cases. The protein expression is tenfold higher in the glioblastoma of patient 1 than in her first breast carcinoma, and twice higher in patient 2. In agreement with the high protein expression level in the GBM, BRCA1 promoter methylation was not observed in these tumours. In these two cases, despite of a BRCA1 pathogenic germline mutation, the tumour-suppressor protein expression is maintained in GBM, suggesting that the BRCA1 mutation is not instrumental for the GBM development. [less ▲]

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See detailEvaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers.
Boukerroucha, Meriem ULiege; Josse, Claire ULiege; El Guendi, Sonia ULiege et al

in BMC Cancer (2015), 15(1), 755

BACKGROUND: The BRCA1 gene plays a key role in triple negative breast cancers (TNBCs), in which its expression can be lost by multiple mechanisms: germinal mutation followed by deletion of the second ... [more ▼]

BACKGROUND: The BRCA1 gene plays a key role in triple negative breast cancers (TNBCs), in which its expression can be lost by multiple mechanisms: germinal mutation followed by deletion of the second allele; negative regulation by promoter methylation; or miRNA-mediated silencing. This study aimed to establish a correlation among the BRCA1-related molecular parameters, tumor characteristics and clinical follow-up of patients to find new prognostic factors. METHODS: BRCA1 protein and mRNA expression was quantified in situ in the TNBCs of 69 patients. BRCA1 promoter methylation status was checked, as well as cytokeratin 5/6 expression. Maintenance of expressed BRCA1 protein interaction with BARD1 was quantified, as a marker of BRCA1 functionality, and the tumor expression profiles of 27 microRNAs were determined. RESULTS: miR-548c-5p was emphasized as a new independent prognostic factor in TNBC. A combination of the tumoral expression of miR-548c and three other known prognostic parameters (tumor size, lymph node invasion and CK 5/6 expression status) allowed for relapse prediction by logistic regression with an area under the curve (AUC) = 0.96. BRCA1 mRNA and protein in situ expression, as well as the amount of BRCA1 ligated to BARD1 in the tumor, lacked any associations with patient outcomes, likely due to high intratumoral heterogeneity, and thus could not be used for clinical purposes. CONCLUSIONS: In situ BRCA1-related expression parameters could be used for clinical purposes at the time of diagnosis. In contrast, miR-548c-5p showed a promising potential as a prognostic factor in TNBC. [less ▲]

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See detailExome sequencing of tumors: relevance in copy-number alteration (CNA) analysis and fixed tissue samples.
Wenric, Stéphane ULiege; JOSSE, Claire ULiege; Fasquelle, Corinne ULiege et al

Poster (2013, March 15)

Genomic DNA has been extracted from both cryopreserved and formalin-fixed paraffin-embedded forms of 2 different tumor samples (triple negative, and Her2+). Exome sequencing has been performed on all 4 ... [more ▼]

Genomic DNA has been extracted from both cryopreserved and formalin-fixed paraffin-embedded forms of 2 different tumor samples (triple negative, and Her2+). Exome sequencing has been performed on all 4 forms, as well as SNP and CNA detection. A comparison of the various metrics and results related to the sequencing, mapping, and variants detection has been done, outlining what can, and can’t be done with exome data sequenced from cryopreserved and FFPE tissue. [less ▲]

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