Splicing patterns of type XI collagen transcripts act as molecular markers for osteochondrogenic tumors

Primary transcripts for three distinct α chains of the type XI collagen molecule (α1(XI), α2(XI) and α3(XI)) undergo tissue-specific alternative splicing during the process of osteochondrogenesis. In the present study, we analyzed the splicing patterns of type XI collagen genes in osteochondrogenic tumors as well as in various normal tissues using the reverse transcription-polymerase chain reaction method. Analysis of normal subjects revealed the coordinated expression of short α1(XI), α2(XI) and α3(XI) transcripts in the normal differentiated cartilage. Osteochondroma followed this pattern, reflecting the highly chondrogenic phenotype of this benign tumor. Another benign tumor, chondroblastoma, exclusively expressed the long α1(XI) transcript, probably reflecting the lack of a chondrogenic nature. Among malignant chondrogenic tumors, the splicing patterns of type XI collagen transcripts were more complex, showing dissociated expression of long α1(XI) and short α2(XI) mRNAs. This expression pattern may reflect heterogeneous cell populations and may also reflect various levels of cell differentiation in malignant tumors. In addition, short α3(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 and splicing analysis may therefore be a useful marker for chondrogenic tumors.