A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value

Brian A. Walker, Paola E. Leone, Laura Chiecchio, Nicholas J. Dickens, Matthew W. Jenner, Kevin D. Boyd, David C. Johnson, David Gonzalez, Gian Paolo Dagrada, Rebecca K M Protheroe, Zoe J. Konn, David M. Stockley, Walter M. Gregory, Faith E. Davies, Fiona M. Ross, Gareth J. Morgan

Research output: Contribution to journalArticle

188 Citations (Scopus)

Abstract

To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.

Original languageEnglish
JournalBlood
Volume116
Issue number15
DOIs
Publication statusPublished - Oct 14 2010

Fingerprint

Genes
Loss of Heterozygosity
Nucleotide Mapping
Histone Code
Uniparental Disomy
Polymorphism
Multiple Myeloma
Fluorescence In Situ Hybridization
Histones
Single Nucleotide Polymorphism
Cell Cycle
Nucleotides
Fluorescence
Cells
Apoptosis
DNA

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Walker, B. A., Leone, P. E., Chiecchio, L., Dickens, N. J., Jenner, M. W., Boyd, K. D., ... Morgan, G. J. (2010). A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. Blood, 116(15). https://doi.org/10.1182/blood-2010-04-279596

A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. / Walker, Brian A.; Leone, Paola E.; Chiecchio, Laura; Dickens, Nicholas J.; Jenner, Matthew W.; Boyd, Kevin D.; Johnson, David C.; Gonzalez, David; Dagrada, Gian Paolo; Protheroe, Rebecca K M; Konn, Zoe J.; Stockley, David M.; Gregory, Walter M.; Davies, Faith E.; Ross, Fiona M.; Morgan, Gareth J.

In: Blood, Vol. 116, No. 15, 14.10.2010.

Research output: Contribution to journalArticle

Walker, BA, Leone, PE, Chiecchio, L, Dickens, NJ, Jenner, MW, Boyd, KD, Johnson, DC, Gonzalez, D, Dagrada, GP, Protheroe, RKM, Konn, ZJ, Stockley, DM, Gregory, WM, Davies, FE, Ross, FM & Morgan, GJ 2010, 'A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value', Blood, vol. 116, no. 15. https://doi.org/10.1182/blood-2010-04-279596
Walker, Brian A. ; Leone, Paola E. ; Chiecchio, Laura ; Dickens, Nicholas J. ; Jenner, Matthew W. ; Boyd, Kevin D. ; Johnson, David C. ; Gonzalez, David ; Dagrada, Gian Paolo ; Protheroe, Rebecca K M ; Konn, Zoe J. ; Stockley, David M. ; Gregory, Walter M. ; Davies, Faith E. ; Ross, Fiona M. ; Morgan, Gareth J. / A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. In: Blood. 2010 ; Vol. 116, No. 15.
@article{8d01b4c81f874f9a9d84b1b62952e002,
title = "A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value",
abstract = "To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30{\%}), 6q (33{\%}), 8p (25{\%}), 12p (15{\%}), 13q (59{\%}), 14q (39{\%}), 16q (35{\%}), 17p (7{\%}), 20 (12{\%}), and 22 (18{\%}). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8{\%}), 16q (9{\%}), and X (20{\%}), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.",
author = "Walker, {Brian A.} and Leone, {Paola E.} and Laura Chiecchio and Dickens, {Nicholas J.} and Jenner, {Matthew W.} and Boyd, {Kevin D.} and Johnson, {David C.} and David Gonzalez and Dagrada, {Gian Paolo} and Protheroe, {Rebecca K M} and Konn, {Zoe J.} and Stockley, {David M.} and Gregory, {Walter M.} and Davies, {Faith E.} and Ross, {Fiona M.} and Morgan, {Gareth J.}",
year = "2010",
month = "10",
day = "14",
doi = "10.1182/blood-2010-04-279596",
language = "English",
volume = "116",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "15",

}

TY - JOUR

T1 - A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value

AU - Walker, Brian A.

AU - Leone, Paola E.

AU - Chiecchio, Laura

AU - Dickens, Nicholas J.

AU - Jenner, Matthew W.

AU - Boyd, Kevin D.

AU - Johnson, David C.

AU - Gonzalez, David

AU - Dagrada, Gian Paolo

AU - Protheroe, Rebecca K M

AU - Konn, Zoe J.

AU - Stockley, David M.

AU - Gregory, Walter M.

AU - Davies, Faith E.

AU - Ross, Fiona M.

AU - Morgan, Gareth J.

PY - 2010/10/14

Y1 - 2010/10/14

N2 - To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.

AB - To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.

UR - http://www.scopus.com/inward/record.url?scp=77957949804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957949804&partnerID=8YFLogxK

U2 - 10.1182/blood-2010-04-279596

DO - 10.1182/blood-2010-04-279596

M3 - Article

VL - 116

JO - Blood

JF - Blood

SN - 0006-4971

IS - 15

ER -