Genome profiling of ovarian adenocarcinomas using pangenomic BACs microarray comparative genomic hybridization

Caserta, Donatella; Benkhalifa, Moncef; Baldi, Marina; Fiorentino, Francesco; Qumsiyeh, Mazin B.; Mangino, Massimo

doi:10.1186/1755-8166-1-10

Cited by 14 publications

(11 citation statements)

References 52 publications

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“…The results were confirmed by univariate and multivariate Cox analysis, were TAI was included as a continuous variable. The aberration patterns in the two cohorts, determined by two different gene-centred platforms, were highly concordant and consistent with those reported by others [14], [15], [20] and with data from The Cancer Genome Atlas project [7].…”

Section: Discussionsupporting

confidence: 88%

High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival

et al. 2013

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Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of genomic instability in predominantly high-grade serous ovarian cancers (SOC) using two independent datasets, generated in Norway (n = 74) and Australia (n = 70), respectively. Genomic instability was quantified by the Total Aberration Index (TAI), a measure of the abundance and genomic size of copy number changes in a tumour. In the Norwegian cohort, patients with TAI above the median revealed significantly prolonged overall survival (p<0.001) and progression-free survival (p<0.05). In the Australian cohort, patients with above median TAI showed prolonged overall survival (p<0.05) and moderately, but not significantly, prolonged progression-free survival. Results were confirmed by univariate and multivariate Cox regression analyses with TAI as a continuous variable. Our results provide further evidence supporting an association between high level of genomic instability and prolonged survival of high-grade SOC patients, possibly as disturbed genome integrity may lead to increased sensitivity to chemotherapeutic agents.

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Section: Discussionsupporting

confidence: 88%

High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival

et al. 2013

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“…The microarrays contain more than 1200 BAC probes for the majority of "new" and "old" microdeletion/microduplication syndromes (for the description see [2,3,5,7]), about 900 BAC probes — subtelomeric regions, about 100 BAC probes — percintromeric chromosomal regions, 621 BAC probes — chromosome X, and about 2000 BAC probes — remaining euchromatic chromosomal regions, allowing the whole genome to be scanned with a resolution of at least 1 Mb. DNA labelling, hybridization, detection and data analysis was made according to previously described protocols [46] and to manufacturers’ instructions.…”

Section: Methodsmentioning

confidence: 99%

Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies

Iourov

Куринная

et al. 2012

Mol Cytogenet

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BackgroundArray comparative genomic hybridization (CGH) has been repeatedly shown to be a successful tool for the identification of genomic variations in a clinical population. During the last decade, the implementation of array CGH has resulted in the identification of new causative submicroscopic chromosome imbalances and copy number variations (CNVs) in neuropsychiatric (neurobehavioral) diseases. Currently, array-CGH-based technologies have become an integral part of molecular diagnosis and research in individuals with neuropsychiatric disorders and children with intellectual disability (mental retardation) and congenital anomalies. Here, we introduce the Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies analyzed by BAC array CGH and a novel bioinformatic strategy.ResultsAmong 54 individuals highly selected according to clinical criteria and molecular and cytogenetic data (from 2426 patients evaluated cytogenetically and molecularly between November 2007 and May 2012), chromosomal imbalances were detected in 26 individuals (48%). In two patients (4%), a previously undescribed condition was observed. The latter has been designated as meiotic (constitutional) genomic instability resulted in multiple submicroscopic rearrangements (including CNVs). Using bioinformatic strategy, we were able to identify clinically relevant CNVs in 15 individuals (28%). Selected cases were confirmed by molecular cytogenetic and molecular genetic methods. Eight out of 26 chromosomal imbalances (31%) have not been previously reported. Among them, three cases were co-occurrence of subtle chromosome 9 and 21 deletions.ConclusionsWe conducted an array CGH study of Russian patients suffering from intellectual disability, autism, epilepsy and congenital anomalies. In total, phenotypic manifestations of clinically relevant genomic variations were found to result from genomic rearrangements affecting 1247 disease-causing and pathway-involved genes. Obviously, a significantly lesser part of them are true candidates for intellectual disability, autism or epilepsy. The success of our preliminary array CGH and bioinformatic study allows us to expand the cohort. According to the available literature, this is the first comprehensive array CGH evaluation of a Russian cohort of children with neuropsychiatric disorders and congenital anomalies.

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“…Technical performance of array CGH (DNA labeling, hybridization, detection, and data analysis) was made according to previously described protocols [4, 10, 11] and to manufacturers' instructions. Array CGH has revealed an interstitial deletion in 20q11.21 spanning from 29,392,835 to 32,017,043 (confirmed by four BAC probes: RP5-1018D12, RP5-836N17, RP5-1085F17, and RP5-1125A11 in two reverse assays).…”

Section: Case Presentation and Methodsmentioning

confidence: 99%

An Interstitial 20q11.21 Microdeletion Causing Mild Intellectual Disability and Facial Dysmorphisms

Iourov

Vorsanova

Куринная

et al. 2013

Case Reports in Genetics

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We report a case of an interstitial chromosome 20q11.21 microdeletion in a 7-year-old male child presenting with mild intellectual disability and facial dysmorphisms. Array comparative genomic hybridization (CGH) has shown that the deletion resulted in the loss of 68 genes, among which 5 genes (COX4I2, MYLK2, ASXL1, DNMT3B, and SNTA1) are disease causing. The size of the deletion was estimated to span 2.6 Mb. Only three cases of deletions encompassing this chromosomal region have been reported. The phenotype of the index patient was found to resemble the mildest cases of Bohring-Opitz syndrome that is caused by ASXL1 mutations. An in silico evaluation of the deleted genomic region has shown that benign genomic variations have never been observed to affect the ASXL1 gene, in contrast to the other disease-causing genes. As a result, it was suggested that ASXL1 loss is likely to be the main cause of the phenotypic manifestations. The present case report indicates that a loss of the disease-causing gene can produce a milder phenotype of a single gene condition.

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Genome profiling of ovarian adenocarcinomas using pangenomic BACs microarray comparative genomic hybridization

Cited by 14 publications

References 52 publications

High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival

High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival

Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies

An Interstitial 20q11.21 Microdeletion Causing Mild Intellectual Disability and Facial Dysmorphisms

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