Comprehensive analysis of 20q13 genes in ovarian cancer identifies ADRM1 as amplification target.
Approximately 25,000 ovarian cancers are diagnosed in the US annually, and 75% of cases are in the advanced stage when they are largely incurable. There is a critical need for improved early detection tools and development of novel treatments. Because chromosome band 20q13 is a commonly DNA amplified region in ovarian cancer and increase in 20q13 copy number may be an early event, we examined the DNA amplification and RNA expression pattern of 239 microarray probes mapping to this region with the goal of identifying gene(s) associated with ovarian cancer. Using Agilent expression microarray analysis and FISH to tumor tissue arrays, we narrowed the candidates to 19 genes that were consistently overexpressed in a subset of tumors amplified for both ZNF217 and TPD54, although, interestingly the candidates do not include these two amplified genes. Unsupervised clustering of 225 ovarian samples with respect to RNA expression of these 19 genes allowed identification of a 20q-amplified subset of 51 (23%) tumors and this subset was significantly correlated with poor outcome. Of the 19 candidate genes in this subset, ADRM1 overexpression was the most highly correlated with amplification, was amplified in a higher percentage of tumors than ZNF217 and TPD54, and was significantly upregulated with respect to stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlates significantly with shorter time to recurrence and overall survival. Functional analysis is now warranted to determine whether ADRM1 is a target for early screening and/or therapy for ovarian cancer.
Fejzo
Marlena S
MS
Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA. mfejzo@mednet.ucla.edu
Dering
Judy
J
Ginther
Chuck
C
Anderson
Lee
L
Ramos
Lilian
L
Walsh
Christine
C
Karlan
Beth
B
Slamon
Dennis J
DJ
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D015152:Blotting, Northern; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D015996:Survival Rate; D013997:Time Factors; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
C500781:ADRM1 protein, human; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C486414:TPD52L2 protein, human; D015534:Trans-Activators; C113698:ZNF217 protein, human