Ap. Manning et al., Expression of FHIT in primary cultures of human epithelial ovarian tumors and malignant ovarian ascites, MOL CARCINO, 24(3), 1999, pp. 218-225
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.