NOVEL CD44 MESSENGER-RNA ISOFORMS IN HUMAN THYROID AND BREAST TISSUESFEATURE UNUSUAL SEQUENCE REARRANGEMENTS

CD44 is a family of cell surface proteins implicated in adhesion inter actions and tumor metastasis. Multiple CD44 mRNA isoforms arise from a lternative splicing of variant exons (termed v1-v10), We recently disc overed a novel CD44 mRNA isoform in human papillary thyroid cancers fe aturing a junction beta een subsegments of exons 4 and 13 (v8), The se quence ACAG was repeated at both the donor and acceptor sites in the g enomic DNA (G, Ermak et nl,, Cancer Res., id: 1037-1042, 1996), We use d reverse transcription-PCR to characterize expression of this isoform in a panel of thyroid lesions, In addition, we assayed three cryopres erved human breast cancers and two samples of normal breast tissue (fr om female subjects who had undergone cosmetic mammoplasty) to determin e whether a similar isoform is present in breast carcinomas, Levels of the novel isoform were up-regulated in 88% of the goiters, adenomas, and papillary cancers, but were undetectable in cases of thyroiditis a nd absent or low level in four samples of normal thyroid tissue, The t hree breast cancers each yielded a 546-bp PCR product that was not det ected in normal breast tissue, The PCR product from one of the breast cancers was cloned, and sequence analysis revealed a novel mRNA isofor m featuring a junction between exon 3 and an internal site within exon 13 (v8), The sequence GCTTCAG was repeated at both the donor and acce ptor sites in the genomic DNA, These results show that human thyroid a nd breast tissues contain novel CD44 mRNA isoforms featuring unusual r earrangements at repeated sequences, Further studies are warranted to determine whether the expression of this class of isoforms correlates with growth status.