Rapid detection of genomic imbalances using micro-arrays consisting of pooled BACs covering all human chromosome arms

Knijnenburg, Jeroen; Burg, Marja van der; Nilsson, Philomeen; Amstel, Hans Kristian Ploos van; Tanke, Hans J.; Szuhai, Károly

doi:10.1093/nar/gni161

Cited by 14 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nick translation labelled, large genomic insert clones from the library used for the array-CGH [ 17 ] with about 1 Mb spacing were used to map the translocation breakpoints of the involved chromosomes. Consecutive pair-wised hybridisations using distal and proximal probes relative to the estimated breakpoints were selected until a probe with split signal was observed.…”

Section: Methodsmentioning

confidence: 99%

A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

Romeo

Szuhai

Nishimori³

et al. 2009

BMC Cancer

View full text Add to dashboard Cite

BackgroundChondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed. Methods: We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH) karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH). Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases.ResultsA balanced t(5;17)(p15;q22-23) was identified. In the index case, interphase FISH showed that the translocation was present only in mononucleated cells and was absent in the characteristic multinucleated giant cells. The t(5;17) translocation was not observed in the other cases studied. The breakpoint in 5p15 occurred close to the steroid reductase 5α1 (SRD5A1) gene. Expression of the protein was found in all cases tested. Similar expression was found for the sex steroid signalling-related molecules oestrogen receptor alpha and aromatase, while androgen receptors were only found in isolated cells in a few cases. The breakpoint in 17q22-23 was upstream of the carbonic anhydrase × (CA10) gene region and possibly involved gene-regulatory elements, which was indicated by the lack of CA10 protein expression in the index case. All other cases showed variable levels of CA10 expression, with low expression in three cases.ConclusionWe report a novel t(5;17)(p15;q22-23) translocation in chondroblastoma without involvement of any of the two chromosomal regions in other cases studied. Our results indicate that the characteristic multinucleated giant cells in chondroblastoma do not have the same clonal origin as the mononuclear population, as they do not harbour the same translocation. We therefore hypothesise that they might be either reactive or originate from a distinct neoplastic clone, although the occurrence of two distinct clones is unlikely. Impairment of the CA10 gene might be pathogenetically relevant, as low expression was found in four cases. Diffuse expression of SRD5A1 and sex steroid signalling-related molecules confirms their role in neoplastic chondrogenesis.

show abstract

Section: Methodsmentioning

confidence: 99%

A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

Romeo

Szuhai

Nishimori³

et al. 2009

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Array printing, hybridization, image acquisition procedures, data extraction, and normalizations were performed as previously described. 15,16 Further analysis and averaging of the triplicate spotted clones was performed with CGH Analyzer MeV (University of Pennsylvania, Abramson Cancer Research Institute). 17 …”

Section: Array Comparative Genomic Hybridization (Cgh)mentioning

confidence: 99%

Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma

Romeo

Duim

Bridge

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

Chondromyxoid fibroma (CMF) is an uncommon benign cartilaginous tumor of bone usually occurring during the second decade of life. CMF is associated with recurrent rearrangements of chromosome bands 6p23-25, 6q12-15, and 6q23-27. To delineate further the role and frequency of the involvement of three candidate regions (6q13, 6q23.3 and 6q24) in the pathogenesis of CMF, we studied a group of 43 cases using a molecular cytogenetic approach. Fluorescence in situ hybridization with probe sets bracketing the putative breakpoint regions was performed in 30 cases. The expression level of nearby candidate genes was studied by immunohistochemistry and quantitative RT-PCR in 24 and 23 cases, respectively. Whole-genome copy number screening was performed by array comparative genomic hybridization in 16 cases. Balanced and unbalanced rearrangements of 6q13 and 6q23.3 occurred in six and five cases, respectively, and a hemizygous deletion in 6q24 was found in five cases. Two known tumor suppressor genes map to the latter region: PLAGL1 and UTRN. However, neither of these two genes nor BCLAF1 and COL12A1, respectively located in 6q23.3 and 6q13, showed altered expression. Therefore, although rearrangements of chromosomal regions 6q13, 6q23.3, and 6q24 are common in CMF, the complexity of the changes precludes the use of a single fluorescence in situ hybridization probe set as an adjunct diagnostic tool. These data indicate that the genetic alterations in CMF are heterogeneous and are likely a result of a cryptic rearrangement beyond the resolution level of combined binary ratio fluorescence in situ hybridization or a point mutation.

show abstract

“…Micro arrays provide distinct advantages over conventional and molecular cytogenetics (pre and post natal, cancer and oncology) analysis because they have the potential to detect the majority of microscopic and sub microscopic chromosomes changes from any DNA sources with or without whole genome amplification [ 30 , 31 ]. Other advantage of A-CGH is the increase in resolution that can be achieved compared to chromosome-based CGH.…”

Section: Introductionmentioning

confidence: 99%

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

Caserta¹,

Benkhalifa²,

Baldi³

et al. 2008

Mol Cytogenet

View full text Add to dashboard Cite

Background: Routine cytogenetic investigations for ovarian cancers are limited by culture failure and poor growth of cancer cells compared to normal cells. Fluorescence in situ Hybridization (FISH) application or classical comparative genome hybridization techniques are also have their own limitations in detecting genome imbalance especially for small changes that are not known ahead of time and for which FISH probes could not be thus designed.

show abstract

Rapid detection of genomic imbalances using micro-arrays consisting of pooled BACs covering all human chromosome arms

Cited by 14 publications

References 15 publications

A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma

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

Contact Info

Product

Resources

About