SPLICING PATTERNS OF TYPE-XI COLLAGEN TRANSCRIPTS ACT AS MOLECULAR MARKERS FOR OSTEOCHONDROGENIC TUMORS

Primary transcripts for three distinct a chains of the type XI collage n molecule (alpha 1(XI), alpha 2(XI) and alpha 3(XI)) undergo tissue-s pecific alternative splicing during the process of osteochondrogenesis . In the present study, we analyzed the splicing patterns of type XI c ollagen genes in osteochondrogenic tumors as well as in various normal tissues using the reverse transcription-polymerase chain reaction met hod. Analysis of normal subjects revealed the coordinated expression o f short alpha 1(XI), alpha 2(XI) and alpha 3(XI) transcripts in the no rmal differentiated cartilage, Osteochondroma followed this pattern, r eflecting the highly chondrogenic phenotype of this benign tumor. Anot her benign tumor, chondroblastoma, exclusively expressed the long alph a 1(XI) transcript, probably reflecting the lack of a chondrogenic nat ure. Among malignant chondrogenic tumors, the splicing patterns of typ e XI collagen transcripts were more complex, showing dissociated expre ssion of long alpha 1(XI) and short alpha 2(XI) mRNAs. This expression pattern may reflect heterogeneous cell populations and may also refle ct various levels of cell differentiation in malignant tumors. In addi tion, short alpha 3(XI) expression switched to the long transcript as chondrosarcomas became more aggressive. Thus, the alternative splicing of type XI collagen genes seems to be oncodevelopmentally regulated a nd splicing analysis may therefore be a useful marker for chondrogenic tumors. (C) 1998 Elsevier Science Ireland Ltd.