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Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival

Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival
Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival
Purpose: regions on 1p with recurrent deletions in presenting myeloma patients were examined with the purpose of defining the deletions and assessing their survival impact.

Experimental design: gene mapping, gene expression, FISH, and mutation analyses were conducted on patient samples from the MRC Myeloma IX trial and correlated with clinical outcome data.

Results: 1p32.3 was deleted in 11% of cases, and deletion was strongly associated with impaired overall survival (OS) in patients treated with autologous stem cell transplant (ASCT). In patients treated less intensively, del(1)(p32.3) was not associated with adverse progression-free survival (PFS) or OS. The target of homozygous deletions was CDKN2C, however its role in the adverse outcome of cases with hemizygous deletion was less certain. 1p22.1-21.2 was the most frequently deleted region and contained the candidate genes MTF2 and TMED5. No mutations were identified in these genes. 1p12 was deleted in 19% of cases, and deletion was associated with impaired OS in univariate analysis. The target of homozygous deletion was FAM46C, which was mutated in 3.4% of cases. When cases with FAM46C deletion or mutation were considered together, they were strongly associated with impaired OS in the intensive treatment setting.

Conclusion: deletion of 1p32.3 and 1p12 was associated with impaired OS in myeloma patients receiving ASCT. FAM46C was identified as a gene with potential pathogenic and prognostic significance based on the occurrence of recurrent homozygous deletions and mutations
1078-0432
7776-7784
Boyd, Kevin D.
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Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Walker, Brian A.
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Wardell, Christopher P.
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Tapper, William J.
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Chiecchio, Laura
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Dagrada, Gian Paolo
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Konn, Zoe J.
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Gregory, Walter M.
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Jackson, Graham H.
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Child, J. Anthony
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Davies, Faith E.
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Morgan, Gareth J.
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NCRI Haematology Oncology Studies Group
Boyd, Kevin D.
20bdd6c8-3f06-4cab-9e12-99903ec18129
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Walker, Brian A.
7e45e107-ca85-4368-8673-7177f2328405
Wardell, Christopher P.
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Tapper, William J.
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Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Dagrada, Gian Paolo
a6e0f6d8-2aa8-4cda-a595-7d75bc5cacf8
Konn, Zoe J.
525b4648-7c88-488a-aefa-0018ac485eb4
Gregory, Walter M.
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Jackson, Graham H.
82e8cc2d-7530-4b02-8f92-176f47451839
Child, J. Anthony
1a7a739b-5295-4818-a455-3c67d9020abc
Davies, Faith E.
9ea9e143-ac51-431b-8cb5-57b8dc0a38af
Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939

Boyd, Kevin D., Ross, Fiona M., Walker, Brian A., Wardell, Christopher P., Tapper, William J., Chiecchio, Laura, Dagrada, Gian Paolo, Konn, Zoe J., Gregory, Walter M., Jackson, Graham H., Child, J. Anthony, Davies, Faith E. and Morgan, Gareth J. , NCRI Haematology Oncology Studies Group (2011) Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival. Clinical Cancer Research, 17 (24), 7776-7784. (doi:10.1158/1078-0432.CCR-11-1791). (PMID:21994415)

Record type: Article

Abstract

Purpose: regions on 1p with recurrent deletions in presenting myeloma patients were examined with the purpose of defining the deletions and assessing their survival impact.

Experimental design: gene mapping, gene expression, FISH, and mutation analyses were conducted on patient samples from the MRC Myeloma IX trial and correlated with clinical outcome data.

Results: 1p32.3 was deleted in 11% of cases, and deletion was strongly associated with impaired overall survival (OS) in patients treated with autologous stem cell transplant (ASCT). In patients treated less intensively, del(1)(p32.3) was not associated with adverse progression-free survival (PFS) or OS. The target of homozygous deletions was CDKN2C, however its role in the adverse outcome of cases with hemizygous deletion was less certain. 1p22.1-21.2 was the most frequently deleted region and contained the candidate genes MTF2 and TMED5. No mutations were identified in these genes. 1p12 was deleted in 19% of cases, and deletion was associated with impaired OS in univariate analysis. The target of homozygous deletion was FAM46C, which was mutated in 3.4% of cases. When cases with FAM46C deletion or mutation were considered together, they were strongly associated with impaired OS in the intensive treatment setting.

Conclusion: deletion of 1p32.3 and 1p12 was associated with impaired OS in myeloma patients receiving ASCT. FAM46C was identified as a gene with potential pathogenic and prognostic significance based on the occurrence of recurrent homozygous deletions and mutations

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e-pub ahead of print date: October 2011
Published date: 15 December 2011
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 337725
URI: https://eprints.soton.ac.uk/id/eprint/337725
ISSN: 1078-0432
PURE UUID: 6354eb3f-4cb6-4b85-ac39-6a987230d290

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Date deposited: 02 May 2012 13:32
Last modified: 16 Jul 2019 22:06

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Contributors

Author: Kevin D. Boyd
Author: Fiona M. Ross
Author: Brian A. Walker
Author: Christopher P. Wardell
Author: Laura Chiecchio
Author: Gian Paolo Dagrada
Author: Zoe J. Konn
Author: Walter M. Gregory
Author: Graham H. Jackson
Author: J. Anthony Child
Author: Faith E. Davies
Author: Gareth J. Morgan

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