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Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia

BACKGROUND: Advances made in the area of microarray comparative genomic hybridization (aCGH) have enabled the interrogation of the entire genome at a previously unattainable resolution. This has lead to the discovery of a novel class of alternative entities called large-scale copy number variations...

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Autores principales: Braude, Ilan, Vukovic, Bisera, Prasad, Mona, Marrano, Paula, Turley, Stefanie, Barber, Dwayne, Zielenska, Maria, Squire, Jeremy A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550726/
https://www.ncbi.nlm.nih.gov/pubmed/16756668
http://dx.doi.org/10.1186/1471-2164-7-138
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author Braude, Ilan
Vukovic, Bisera
Prasad, Mona
Marrano, Paula
Turley, Stefanie
Barber, Dwayne
Zielenska, Maria
Squire, Jeremy A
author_facet Braude, Ilan
Vukovic, Bisera
Prasad, Mona
Marrano, Paula
Turley, Stefanie
Barber, Dwayne
Zielenska, Maria
Squire, Jeremy A
author_sort Braude, Ilan
collection PubMed
description BACKGROUND: Advances made in the area of microarray comparative genomic hybridization (aCGH) have enabled the interrogation of the entire genome at a previously unattainable resolution. This has lead to the discovery of a novel class of alternative entities called large-scale copy number variations (CNVs). These CNVs are often found in regions of closely linked sequence homology called duplicons that are thought to facilitate genomic rearrangements in some classes of neoplasia. Recently, it was proposed that duplicons located near the recurrent translocation break points on chromosomes 9 and 22 in chronic myeloid leukemia (CML) may facilitate this tumor-specific translocation. Furthermore, ~15–20% of CML patients also carry a microdeletion on the derivative 9 chromosome (der(9)) and these patients have a poor prognosis. It has been hypothesised that der(9) deletion patients have increased levels of chromosomal instability. RESULTS: In this study aCGH was performed and identified a CNV (RP11-125A5, hereafter called CNV14q12) that was present as a genomic gain or loss in 10% of control DNA samples derived from cytogenetically normal individuals. CNV14q12 was the same clone identified by Iafrate et al. as a CNV. Real-time polymerase chain reaction (Q-PCR) was used to determine the relative frequency of this CNV in DNA from a series of 16 CML patients (both with and without a der(9) deletion) together with DNA derived from 36 paediatric solid tumors in comparison to the incidence of CNV in control DNA. CNV14q12 was present in ~50% of both tumor and CML DNA, but was found in 72% of CML bearing a der(9) microdeletion. Chi square analysis found a statistically significant difference (p ≤ 0.001) between the incidence of this CNV in cancer and normal DNA and a slightly increased incidence in CML with deletions in comparison to those CML without a detectable deletion. CONCLUSION: The increased incidence of CNV14q12 in tumor samples suggests that either acquired or inherited genomic variation of this new class of variation may be associated with onset or progression of neoplasia.
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spelling pubmed-15507262006-08-19 Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia Braude, Ilan Vukovic, Bisera Prasad, Mona Marrano, Paula Turley, Stefanie Barber, Dwayne Zielenska, Maria Squire, Jeremy A BMC Genomics Research Article BACKGROUND: Advances made in the area of microarray comparative genomic hybridization (aCGH) have enabled the interrogation of the entire genome at a previously unattainable resolution. This has lead to the discovery of a novel class of alternative entities called large-scale copy number variations (CNVs). These CNVs are often found in regions of closely linked sequence homology called duplicons that are thought to facilitate genomic rearrangements in some classes of neoplasia. Recently, it was proposed that duplicons located near the recurrent translocation break points on chromosomes 9 and 22 in chronic myeloid leukemia (CML) may facilitate this tumor-specific translocation. Furthermore, ~15–20% of CML patients also carry a microdeletion on the derivative 9 chromosome (der(9)) and these patients have a poor prognosis. It has been hypothesised that der(9) deletion patients have increased levels of chromosomal instability. RESULTS: In this study aCGH was performed and identified a CNV (RP11-125A5, hereafter called CNV14q12) that was present as a genomic gain or loss in 10% of control DNA samples derived from cytogenetically normal individuals. CNV14q12 was the same clone identified by Iafrate et al. as a CNV. Real-time polymerase chain reaction (Q-PCR) was used to determine the relative frequency of this CNV in DNA from a series of 16 CML patients (both with and without a der(9) deletion) together with DNA derived from 36 paediatric solid tumors in comparison to the incidence of CNV in control DNA. CNV14q12 was present in ~50% of both tumor and CML DNA, but was found in 72% of CML bearing a der(9) microdeletion. Chi square analysis found a statistically significant difference (p ≤ 0.001) between the incidence of this CNV in cancer and normal DNA and a slightly increased incidence in CML with deletions in comparison to those CML without a detectable deletion. CONCLUSION: The increased incidence of CNV14q12 in tumor samples suggests that either acquired or inherited genomic variation of this new class of variation may be associated with onset or progression of neoplasia. BioMed Central 2006-06-06 /pmc/articles/PMC1550726/ /pubmed/16756668 http://dx.doi.org/10.1186/1471-2164-7-138 Text en Copyright © 2006 Braude et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Braude, Ilan
Vukovic, Bisera
Prasad, Mona
Marrano, Paula
Turley, Stefanie
Barber, Dwayne
Zielenska, Maria
Squire, Jeremy A
Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia
title Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia
title_full Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia
title_fullStr Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia
title_full_unstemmed Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia
title_short Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia
title_sort large scale copy number variation (cnv) at 14q12 is associated with the presence of genomic abnormalities in neoplasia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550726/
https://www.ncbi.nlm.nih.gov/pubmed/16756668
http://dx.doi.org/10.1186/1471-2164-7-138
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