Faculty Opinions recommendation of Array-based comparative genomic hybridization for the genomewide detection of submicroscopic chromosomal abnormalities.

The molecular basis of parathyroid adenomatosis includes defects in the cyclin D1/PRAD1 and MEN1 genes but is, in large part, unknown. To identify new locations of parathyroid oncogenes or tumor suppressor genes, and to further establish the importance of DNA losses described by molecular allelotyping, we performed comparative genomic hybridization (CGH) on a panel of 53 typical sporadic (nonfamilial) parathyroid adenomas. CGH is a new molecular cytogenetic technique in which the entire tumor genome is screened for chromosomal gains and/or losses. Two abnormalities, not previously described, were found recurrently: gain of chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or 9%). Losses were found frequently on 11p (14 of 53, or 26%), as well as 11q (18 of 53, or 34%). Recurrent losses were also seen on chromosomes 1p, 1q, 6q, 9p, 9q, 13q, and 15q, with frequencies ranging from 8–19%. Twenty-four of the 53 adenomas were also extensively analyzed with polymorphic microsatellite markers for allelic losses, either in this study (11 cases) or previously (13 cases). Molecular allelotyping results were highly concordant with CGH results in these tumors (concordance level of 97.5% for all informative markers/chromosome arms examined). In conclusion, CGH has identified the first two known chromosomal gain defects in parathyroid adenomas, suggesting the existence of direct-acting parathyroid oncogenes on chromosomes 16 and 19. CGH has confirmed the locations of putative parathyroid tumor suppressor genes, also defined by molecular allelotyping, on chromosomes 1p, 6q, 9p, 11q, 13q, and 15q. Finally, CGH has provided new evidence favoring the possibility that distinct parathyroid tumor suppressors exist on 1p and 1q, and has raised the possibility of a parathyroid tumor suppressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can identify recurrent genetic abnormalities in hyperparathyroidism, especially chromosomal gains, that other methods do not detect.

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Widespread chromosomal abnormalities in high-grade ductal carcinomain situ of the breast. Comparative genomic hybridization study of pure high-grade DCIS

The Journal of Pathology ◽

10.1002/(sici)1096-9896(199903)187:4<403::aid-path284>3.0.co;2-j ◽

1999 ◽

Vol 187 (4) ◽

pp. 403-409 ◽

Cited By ~ 35

Author(s):

Elizabeth Moore ◽

Hilary Magee ◽

John Coyne ◽

Tom Gorey ◽

Peter A. Dervan

Keyword(s):

Comparative Genomic Hybridization ◽

Chromosomal Abnormalities ◽

Comparative Genomic ◽

High Grade ◽

Hybridization Study ◽

Genomic Hybridization ◽

Ductal Carcinomain Situ ◽

Carcinomain Situ

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Characterization of complex chromosomal abnormalities in uveal melanoma by fluorescence in situ hybridization, spectral karyotyping, and comparative genomic hybridization

Genes Chromosomes and Cancer ◽

10.1002/1098-2264(2000)9999:9999<::aid-gcc1088>3.0.co;2-7 ◽

2001 ◽

Vol 30 (3) ◽

pp. 267-273 ◽

Cited By ~ 38

Author(s):

Nicole C. Naus ◽

Ellen van Drunen ◽

Annelies de Klein ◽

Gregorius P.M. Luyten ◽

Dion A. Paridaens ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Comparative Genomic Hybridization ◽

Uveal Melanoma ◽

Chromosomal Abnormalities ◽

Comparative Genomic ◽

Spectral Karyotyping ◽

Genomic Hybridization

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A novel de novo paracentric inversion [inv(20)(q13.1q13.3)] accompanied by an 11q14.3-q21 microdeletion in a pediatric patient with an intellectual disability

Balkan Journal of Medical Genetics ◽

10.2478/bjmg-2018-0016 ◽

2018 ◽

Vol 21 (2) ◽

pp. 63-67

Author(s):

S Zachaki ◽

E Kouvidi ◽

A Mitrakos ◽

L Lazaros ◽

A Pantou ◽

...

Keyword(s):

Mental Retardation ◽

Comparative Genomic Hybridization ◽

Array Comparative Genomic Hybridization ◽

De Novo ◽

Chromosomal Abnormalities ◽

Mendelian Inheritance ◽

Paracentric Inversion ◽

Comparative Genomic ◽

Published Data ◽

Genomic Hybridization

Abstract A novel de novo paracentric inversion of the long arm of chromosome 20 [inv(20)(q13.1q13.3)], detected by conventional karyotyping in a 14-year-old boy with mental retardation is described. Further investigation by array comparative genomic hybridization (aCGH) revealed that the 20q inversion was not accompanied by microdeletions/microduplications containing disease-associated genes near or at the breakpoints. Two deletions at chromosomal regions 11q14.3q21 and 20q12 of 4.5 and 1.97 Mb size, respectively, containing important online Mendelian inheritance in man (OMIM) genes, were detected. The 4.5Mb 11q14.3q21 microdeletion was contained within a region that is involved, in most of the reported cases, with the interstitial 11q deletion and may be related to the mental retardation and developmental delay present in the patient. On the other hand, the published data about the 20q12 microdeletion are very few and it is not possible to correlate this finding with our patient’s phenotype. This case report contributes to the description of a new chromosomal entity, not previously reported, and is therefore important, especially in prenatal diagnosis and management of patients. Array comparative genomic hybridization has proven a useful technique for detecting submicroscopic rearrangements and should be offered prenatally, especially in cases of de novo karyotypically balanced chromosomal inversions or translocations in order to unveil other unbalanced chromosomal abnormalities such as deletions and amplifications.

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Comparative Genomic Hybridization on Immunophenotypically Pure, Flow Sorted Plasmocyte Populations Shows an Improved Detection of Chromosomal Abnormalities in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.3404.3404 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3404-3404

Author(s):

Brigitte Maes ◽

Sabine Franke ◽

Greet Voets ◽

Karen Hensen ◽

Hanne Jongen ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Comparative Genomic Hybridization ◽

Monoclonal Gammopathy ◽

Chromosomal Abnormalities ◽

Oligonucleotide Primer ◽

Comparative Genomic ◽

Genomic Hybridization ◽

Degenerate Oligonucleotide ◽

Undetermined Significance

Abstract Multiple myeloma (MM) is a clonal plasmocyte disorder often preceded by a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). Chromosomal abnormalities in MM are complex, of which some are at present considered the most important prognostic indicators in MM. Their role in the pathogenesis of MM and in the transformation from MGUS towards MM is however not fully understood, at least partly due to the low-level bone marrow infiltration hampering cytogenetic analysis. In this study, a unique combination of techniques was used to allow whole genome screening for numerical chromosomal abnormalities of immunophenotypically pure, aberrant plasmocyte populations selected from the bone marrow by flow cytometry. Fourteen bone marrow samples from patients with either MM (n= 11) (first diagnosis or relapsing) or MGUS (n=3), with plasmocyte percentages as low as 1 % (range 1 – 57 %), were analyzed. Aberrant/monoclonal plasmocyte populations were identified based on the expression of CD56 and/or light chain restriction within a CD138+/CD38++ gate and sorted using a FACSAria® (BD, US). Whole genomic DNA was extracted from the CD56+or−/κ or λ+ plasmocyte populations, amplified with degenerate oligonucleotide primer-PCR and used for comparative genomic hybridization (CGH). CGH results were confirmed by interphase fluorescent in situ hybridization. All cases (MM and MGUS) showed the presence of multiple chromosomal abnormalities with a minimum of 5 each. All chromosomes were at least one time involved. Relapsing MM showed a mean number of chromosomal changes of 10 compared to 7 and 6 in newly diagnosed MM and MGUS cases respectively, suggesting karyotypic instability during the course of the disease. The presence of chromosomal aberrations known to be frequently occurring in MM, was confirmed such as gains of 1q (4/11, 36%), 7q (5/11, 45%) and 5q11-q32 (7/11, 64%) and losses of 13q (6/11, 55 %) and 16q (4/11, 36%). This study also showed a high incidence of chromosomal abnormalities not previously or only rarely described in MM, such as gains of 4q11-q22 (9/11, 82 %) and 8q21-q23 (5/11, 45%) and loss of 20q (5/11, 45 %). Some abnormalities were detected in both MM and MGUS, such as gain of 5q and loss of 16q, and may be considered very early, primary aberrations. Gain of 4q11-q22 was detected in almost all MM cases but in none of the MGUS cases, suggesting this abnormality might be involved in disease progression. These results indicate a higher complexity and diversity of chromosomal abnormalities in both MM and MGUS, than has already been described. CGH on flow sorted, immunophenotypically pure, aberrant plasmocytes allows an adequate genetic analysis of MGUS, which should ultimately result in the identification of genetic changes involved in the transformation of MGUS towards MM.

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