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Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma. Delineation of Breakpoints and Analysis of Candidate Target Genes.

Romeo, Salvatore; Duim, Ronald A J; Bridge, Julia A; Mertens, Fredrik LU ; de Jong, Danielle; Dal Cin, Paola; Wijers-Koster, Pauline M; Debiec-Rychter, Maria; Sciot, Raf and Rosenberg, Andrew E, et al. (2010) In American Journal of Pathology 177(3). p.1365-1376
Abstract
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... (More)
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. (Less)
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American Journal of Pathology
volume
177
issue
3
pages
1365 - 1376
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000281717700032
  • pmid:20696777
  • scopus:77956514684
ISSN
1525-2191
DOI
10.2353/ajpath.2010.091277
language
English
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yes
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efc6c7cf-24be-4a96-9d57-59d136688045 (old id 1665409)
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http://www.ncbi.nlm.nih.gov/pubmed/20696777?dopt=Abstract
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2010-09-14 09:53:09
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2018-05-29 09:43:35
@article{efc6c7cf-24be-4a96-9d57-59d136688045,
  abstract     = {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.},
  author       = {Romeo, Salvatore and Duim, Ronald A J and Bridge, Julia A and Mertens, Fredrik and de Jong, Danielle and Dal Cin, Paola and Wijers-Koster, Pauline M and Debiec-Rychter, Maria and Sciot, Raf and Rosenberg, Andrew E and Szuhai, Karoly and Hogendoorn, Pancras C W},
  issn         = {1525-2191},
  language     = {eng},
  number       = {3},
  pages        = {1365--1376},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma. Delineation of Breakpoints and Analysis of Candidate Target Genes.},
  url          = {http://dx.doi.org/10.2353/ajpath.2010.091277},
  volume       = {177},
  year         = {2010},
}