Absence of evidence for allelic loss or allelic gain for ERCC1 or for XPD in human ovarian cancer cells and tissues.
We have previously reported on mRNA expression of ERCC1, XPA and XPD in human ovarian cancer cells and tissues. Several factors can influence mRNA expression for any given gene. Alterations in gene copy number for ERCC1 and/or XPD have been reported to occur in malignant glioma specimens. Human ovarian cancer cell lines and tissues were therefore examined for evidence of altered gene copy number in selected genes within the nucleotide excision repair (NER) pathway. Six ovarian cancer cell lines were studied: A2780, A2780/CP70, SKOV3, MCAS, QvCar3 and Caov4. Cellular sensitivity to cisplatin varies by more than 1 log between some of these cells. In each of these cell lines, the genes examined included ERCC1, XPA, XPB, XPD, XPG, CSB and p53. Genomic DNA was also extracted from ovarian cancer specimens taken from 22 patients and assessed for evidence of allelic loss and/or allelic gain for ERCC1 and XPD. Twelve of the clinical specimens were from patients with platinum-sensitive tumors and ten were from patients with platinum-resistant tumors. In no case could we demonstrate a reproducible variation in gene copy number in any cell line. Among the human tissues studied, there was one case of allelic gain out of 22 specimens. We therefore conclude that alterations in gene copy number is not a common event in human ovarian cancer. Other mechanisms must be invoked to explain differences in mRNA expression for these genes.
Yu
J J
JJ
Medical Ovarian Cancer Section, Medicine Branch, DCS, National Cancer Institute, Building 10, Room 12N226, Bethesda, MD 20892, USA.
Bicher
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A
Ma
Y K
YK
Bostick-Bruton
F
F
Reed
E
E
D015139:Blotting, Southern; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases; D005260:Female; D018628:Gene Dosage; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010984:Platinum / Q000494:pharmacology; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D010984:Platinum; C071447:ERCC1 protein, human; D004720:Endonucleases; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin