Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses.
OBJECTIVE
Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease.


METHODS
Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance.


RESULTS
Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemo-response data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002).


CONCLUSIONS
These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.
Tsuda
Hiroshi
H
Department of Obstetrics and Gynecology, Laboratory of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ito
Yoichi M
YM
Ohashi
Yasuo
Y
Wong
Kwong-Kwok
KK
Hashiguchi
Yasunori
Y
Welch
William R
WR
Berkowitz
Ross S
RS
Birrer
Michael J
MJ
Mok
Samuel C
SC
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics*; D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009841:Oligonucleotides / Q000235:genetics; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016896:Treatment Outcome
C507640:ABCF2 protein, human; D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D009841:Oligonucleotides; D004247:DNA