[84] Balanced and Unbalanced Rearrangement of Chromosome Arm 6q in Chondromyxoid Fibroma (CMF): Delineation of Breakpoints and Analysis of Candidate Target Genes

S Romeo, RAJ Duim, F Mertens, D De Jong, P Dal Cin, M Debiec-Rychter, R Sciot, A Rosenberg, K Szuhai, PCW Hogendoorn. Leiden University Medical Center, Leiden, Netherlands; Lund University Hospital, Lund, Sweden; Brigham and Women's Hospital, Boston, MA; Catholic University of Leuven, Leuven, Belgium; Massachusetts General Hospital, Boston, MA

Background: CMF is a benign cartilaginous tumour of bone mainly occurring in the second decade of life in long bones. Recurrent rearrangements of chromosomal bands 6p25, 6p23-25, 6q12-15 or 6q23-27 are reported. We aimed to refine location and functional consequences of these rearrangements.
Design: Structural chromosomal aberrations were studied in 7 cases, including 5 not previously reported, by CoBRA-FISH and conventional G-banding. Breakpoints FISH mapping was performed in case L1788. Array CGH was performed on 15 cases to identify additional copy number changes. On the basis of the results 14 cases were further evaluated by interphase FISH. The expression level of candidate genes close to the breakpoints was studied by immunohistochemistry and Q-PCR in 25 and 15 cases, respectively.
Results: The karyotypes in the 5 new cases were:

Number	Description
L1788	46,XX,t(6;17)(q23;p13)
L2367	46,XY,der(6)(6qter->6q2?::6p2?->6q13::6q2?->6q2?::6q13->6qter),del(6)(q13), der(22)t(6;22)(q24;p11)
L2499	46,XY,del(6)(q2?1), -13,der(?)t(?;1)(?;q12)
L2514	46,XY,del(6)(q15q23),del(6)(q1?3q2?5),add(11)(q2?5)
L2515	46,XY,der(6)t(6;10)(p25;p11)t(6;11)(q24;p12),del(6)(q12),der(10)t(6;10)(q12;p11),der(11)t(6;11)(q24;p12)

The other two showed: 46,XY,del(6)(q15),der(6)t(6;6)(q15;q27)inv(6)(p25q13) (L1787); 46,XX,del(6)(?q21?q23),add(7)(q21) (L1789). No copy number changes was found in 12 cases, including L1788, L2367, L1787 and L2515. A small overlapping deletion on 6q24, in the region of UTRN, was found in 4 cases, including L1789 and L2499. FISH mapping showed possible involvement of BCLAF1 on 6q23. No significant expression impairment of these two tumor suppressor genes was found in the evaluated series.
Conclusions: The present study confirmed the nonrandom involvement of chromosome arm 6q in CMF. Both balanced and unbalanced recurrent rearrangements were detected and candidate genes were studied. These data indicate that multiple genes in chromosome 6 are involved in the pathogenesis of CMF.
Category: Bone & Soft Tissue

Tuesday, March 10, 2009 9:30 AM

Poster Session III # 22, Tuesday Morning