Expression of FHIT in primary cultures of human epithelial ovarian tumors and malignant ovarian ascites

Abnormal FHIT gene expression has been reported in a variety of epithelial tumors shown to harbor deletions of chromosome 3p14, the chromosomal assign ment of th is gene. Recently, we described loss of heterozygosity of 3p in a subset of epithelial ovarian cancers. To investigate a potential role of the FHIT gene in ovarian cancer, we examined primary cell cultures derived from normal ovarian surface epithelium, ovarian tumors, and the cellular fr action of malignant ascites to determine the expression of FHIT by using re verse transcription-polymerase chain reaction. Included in this analysis we re four spontaneously immortalized cell lines: three derived from malignant epithelial ovarian tumors (TOV21G, TOV112D, and TOV81D) and one from malig nant ovarian ascites (OV90). OV90 was previously shown to harbor a deletion of the whole p arm of chromosome 3. The FHIT transcript was not detectable in two of 11 primary cultures derived from normal ovarian surface epitheli um or in a primary culture derived from malignant ovarian ascites, whereas the remaining samples (34 malignant, eight borderline, and three benign spe cimens), exhibited identical expression patterns. In each case, this patter n was consistent with the co-expression of a normal FHIT transcript and a s maller transcript. DNA sequencing revealed that the abnormal-sized message lacked exons 4-7 (inclusive), which were deleted at their exact intron-exon splice sites. The aberrant-sized transcript was detectable by Northern blo t analysis. There was no concordance between FHIT expression and loss of he terozygosity at the FHIT locus. Northern blot analysis also revealed that F HIT was differentially expressed, and the spontaneously immortalized cell l ines TOV21G and TOV112D showed the highest level of expression. Because the same reverse transcription-polymerase chain reaction expression pattern wa s observed in both normal and tumor-derived primary cell cultures, these re sults argue against a significant role for FHIT in epithelial ovarian tumor igenesis. Mel. Carcinog. 24:218-225, 1999. (C) 1999 Wiley-Liss, Inc.