[103] Cytogenetic and Molecular Cytogenetic Findings in Chondromyxoid Fibroma: Aberrations of 6q13 Mapped to the COL12A1 Locus by Fluorescence In Situ Hybridization

T Yasuda, J Nishio, KM Kapels, PA Althof, JR Sawyer, JD Reith, JA Bridge. University of Nebraska Medical Center, Omaha, NE; Fukuoka University Chikushino Hospital, Fukuoka, Japan; University of Arkansas, Little Rock, AR; University of Florida College of Medicine, Gainesville, FL

Background: Chondromyxoid fibroma (CMF), a rare benign bone tumor, may be mistaken for chondrosarcoma. Although cytogenetic studies of CMF are few, rearrangements of the long arm of chromosome 6 frequently expressed as an inv(6)(p25q13) are prominent. The objectives of this study were to: 1) broaden the currently available cytogenetic data on this unusual entity by subjecting additional CMFs to karyotypic analysis; 2) further localize the recurrently involved 6q13 breakpoint; and, 3) uncover potential candidate gene(s).
Design: 15 CMF specimens from 13 patients were analyzed utilizing standard cytogenetic analysis. A fluorescence in situ hybridization (FISH)-based positional cloning strategy on CMF abnormal metaphase cells using a series of bacterial and P1 artificial chromosome (BAC/PAC) probe combinations spanning a 6.1 Mb region was employed for narrowing the 6q13 breakpoint. Following identification of the BAC/PAC probe sets most closely approximating the critical 6q13 breakpoint, additional FISH studies were conducted on interphase cells obtained from cytologic touch preparations of 12 CMFs.
Results: Chromosome 6 abnormalities were detected in 9 of the 10 clonally abnormal CMFs. In addition to 6q13 rearrangements, recurrent 6p25 and 6q25 anomalies were detected. FISH studies demonstrated that the definitive 6q13 breakpoint locus was flanked proximally by a RP11-560O20, RP11-536O4 and RP1-238D15 BAC/PAC probe cocktail and distally by a RP11-209D8 and RP1-234P15 BAC/ PAC probe cocktail; a region encompassing the COL12A1 gene locus. Abnormalities of 6q13 were identified by metaphase and/or interphase cell FISH analysis in 2 of 14 (14%) CMFs.
Conclusions: These cytogenetic and molecular cytogenetic findings expand our knowledge of chromosomal alterations in CMF, further localize the critically involved 6q13 breakpoint with identification of COL12A1 as the likely gene candidate, and provide an alternative approach for detecting 6q13 abnormalities in nondividing cells of CMF. The latter could potentially be utilized as an adjunct in diagnostically challenging cases.
Category: Bone & Soft Tissue

Tuesday, March 10, 2009 9:30 AM

Poster Session III # 23, Tuesday Morning