Loss of heterozygosity in the retinoblastoma tumor suppressor gene in skull base chordomas and chondrosarcomas

BACKGROUND The retinoblastoma (Rb) gene is a well characterized tumor suppressor gene in which loss of heterozygosity has been implicated in a number of malignancies including osteosarcoma and breast carcinoma. Chordomas and chondrosarcomas are rare skull base neoplasms with a propensity for local recurrences, resistance to conventional radiotherapy, and a 5%-30% incidence of metastases. Except for the so called ''chondroid chordoma,'' histologic features do not correlate with the clinical behavior or growth patterns of these tumors. No study to date has investigated what role tumor suppressor genes or oncogenes play in the development and continued growth of these rare neoplasms. METHODS In order to evaluate the role of the retinoblastoma tumor suppressor gene in chordomas and chondrosarcomas we screened seven chordomas and two chondrosarcomas located at the skull base for loss of heterozygosity (LOH) of the Rb gene. Genomic DNA was extracted from tumor specimens as well as matched control tissue and utilizing a polymerase chain reaction technique, intron 17 and 20 were amplified from each specimen. The intron 17 product was then digested with the restriction endonuclease X bal followed by electrophoresis on a 1% agrose gel. The intron 20 amplified products were electrophoresed on a nondenaturing 6% polyacrylamide gel, RESULTS We demonstrated LOH at intron 17 of the retinoblastoma gene in 2/7 chordomas and in 0/2 chondrosarcomas. The two chordomas possessing LOH were particularly aggressive tumors demonstrating extensive involvement of the skull base and rapid recurrences following radical resections. CONCLUSIONS Alterations of the Rb gene may play a role in the growth of skull base chordomas with LOH of the Rb gene serving as a marker for more aggressive tumors, This report represents the first study evaluating the Rb gene in chordomas or chondrosarcomas and is the first report of allelic loss of the Rb gene in skull base chordomas. (C) 1997 by Elsevier Science Inc.