[107] Heterogeneous and Complex Rearragements of the Long Arm of Chromosome 6 in Chondromyxoid Fibroma

S Romeo, RAJ Duim, JA Bridge, F Mertens, D De Jong, P Dal Cin, PM Wijers-Koster, M Debiec-Rychter, R Sciot, A Rosenberg, K Szuhai, PCW Hogendoorn. Treviso Reional Hospital, Treviso, Italy; Leiden Univesty Medial Center, Leiden, Netherlands; University of Nebraska Medical Center, Omaha; Lund University Hospital, Lund, Sweden; Brigham and Women's Hospital, Boston; Catholic University of Leuven, Leuven, Belgium; Massachusetts General Hospital, Boston

Background: Chondromyxoid fibroma (CMF) is a benign cartilaginous tumour of bone mainly occurring in the second decade of life. Recurrent chromosomal rearrangements of chromosome bands 6p23-25, 6q12-15 and 6q23-27 have been reported in these tumors. The aim of the study is to further understand the role of these regions in the pathogenesis of CMF.
Design: We collected 42 CMFs and used a panel of molecular cytogenetic tests verified by immunohistochemical staining to investigate the implicated regions of interest . Whole genome copy number screening was performed by array-CGH in 15 cases. Three candidate regions (6q13, 6q23.3 and 6q24) were investigated in detail by FISH probe sets bracketing fine mapped breakpoint regions in 29 cases and the potential diagnostic relevance of any of these regions was analyzed. The expression level of nearby candidate genes was evaluated by immunohistochemistry and Q-RT-PCR in 25 and 26 cases, respectively.
Results: Fourteen of twenty-one cytogenetically analyzed cases had structural aberrations involving chromosome 6. Seventeen of twenty-nine cases (58%) showed no rearrangement at FISH analysis of the breakpoint regions. A common minimal region of deletion was detected in three cases at 6q24 by array-CGH. The hemizygous deletion in 6q24 was verified in all three cases and an additional case was identified. The other two investigated regions showed both balanced as well as unbalanced rearrangements of 6q13 and 6q23.3 in six and five cases, respectively. Expression profiling of the two known tumour suppressor genes (PLAGL1 and UTRN) residing at 6q24 and the BCLAF1, at 6q23.3, showed no changes.
Conclusions: We identified recurrent balanced and unbalanced rearrangements of three bands on chromosome arm 6q in CMF: 6q13, 6q23.3, and 6q24. Based on these results we could conclude that genetic alterations in CMF are heterogeneous; the observed changes may be secondary to either a cryptic translocation or a point mutation. All together rearrangements of these three regions occur in less than half of CMFs, reducing their diagnostic usefulness.
Category: Bone & Soft Tissue

Tuesday, March 23, 2010 2:00 PM

Platform Session: Section E, Tuesday Afternoon


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