Intron 9 retention in gene transcripts suggests involvement of CD44 in the tumorigenesis of ovarian cancer.

Increased or de novo expression of certain CD44 variant isofoms as well as abnormal processing of pre-mRNA of the CD44 gene have been found in different malignant human tumors. Retention of the non-coding intron 9 sequence in CD44 mRNA especially, appears to be a discriminating aberrant splicing pattern in several cancer tissues and cells. We examined the expression of the CD44 intron 9 sequence in the mRNA of 45 permanent ovarian cancer cell lines and in normal ovarian tissue. Abnormal retention of intron 9 was found in 19 (60%) cell lines expressing CD44 std. Normal ovarian tissue as well as all ovarian cancer cells without CD44 s t d expression were found to be negative for intron 9 retention. Our results indicate that besides newly acquired expression of certain CD44 isoforms abnormal retention of the non-coding intron 9 sequence in CD44 gene transcripts is also a common and maybe crucial event in the tumorigenesis of ovarian cancer. Since intron 9 is not retained in normal ovarian tissue this aberration might serve as a marker for human adenocarcinoma of the ovary.