Heterogeneous and complex rearrangements of chromosome arm 6q in chondromyxoid fibroma: Delineation of breakpoints and analysis of candidate target genes

Salvatore Romeo, Ronald A J Duim, Julia A. Bridge, Fredrik Mertens, Danielle De Jong, Paola Dal Cin, Pauline M. Wijers-Koster, Maria Debiec-Rychter, Raf Sciot, Andrew E. Rosenberg, Karoly Szuhai, Pancras C W Hogendoorn

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1365-1376
Number of pages12
JournalAmerican Journal of Pathology
Volume177
Issue number3
DOIs
StatePublished - Sep 2010

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Fibroma
Genetic Association Studies
Chromosomes
Fluorescence In Situ Hybridization
Comparative Genomic Hybridization
Tumor Suppressor Genes
Point Mutation
Cytogenetics
Genes
Immunohistochemistry
Genome
Bone and Bones
Polymerase Chain Reaction
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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; De Jong, Danielle; Dal Cin, Paola; Wijers-Koster, Pauline M.; Debiec-Rychter, Maria; Sciot, Raf; Rosenberg, Andrew E.; Szuhai, Karoly; Hogendoorn, Pancras C W.

In: American Journal of Pathology, Vol. 177, No. 3, 09.2010, p. 1365-1376.

Research output: Contribution to journalArticle

Romeo, S, Duim, RAJ, Bridge, JA, Mertens, F, De Jong, D, Dal Cin, P, Wijers-Koster, PM, Debiec-Rychter, M, Sciot, R, Rosenberg, AE, Szuhai, K & Hogendoorn, PCW 2010, 'Heterogeneous and complex rearrangements of chromosome arm 6q in chondromyxoid fibroma: Delineation of breakpoints and analysis of candidate target genes', American Journal of Pathology, vol. 177, no. 3, pp. 1365-1376. https://doi.org/10.2353/ajpath.2010.091277
Romeo, Salvatore ; Duim, Ronald A J ; Bridge, Julia A. ; Mertens, Fredrik ; De Jong, Danielle ; Dal Cin, Paola ; Wijers-Koster, Pauline M. ; Debiec-Rychter, Maria ; Sciot, Raf ; Rosenberg, Andrew E. ; Szuhai, Karoly ; Hogendoorn, Pancras C W. / Heterogeneous and complex rearrangements of chromosome arm 6q in chondromyxoid fibroma : Delineation of breakpoints and analysis of candidate target genes. In: American Journal of Pathology. 2010 ; Vol. 177, No. 3. pp. 1365-1376.
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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.",
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AU - Dal Cin, Paola

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AU - Debiec-Rychter, Maria

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