Amplicon profiles in ovarian serous carcinomas.
Ovarian serous carcinoma is the most common and lethal type of ovarian cancer and its molecular etiology remains poorly understood. As an ongoing effort to elucidate the pathogenesis of ovarian serous carcinomas, we assessed the DNA copy number changes in 33 high-grade serous carcinomas and 10 low-grade serous tumors by using a genome-wide technique, single nucleotide polymorphism array, performed on affinity-purified tumor cells from fresh surgical specimens. Compared to low-grade tumors, high-grade serous carcinomas showed widespread DNA copy number changes. The most frequent alterations were in loci harboring candidate oncogenes: cyclin E1 (CCNE1), AKT2, Notch3 and PIK3CA as well as in novel loci, including 12p13, 8q24, 12p13 and 12q15. Seven amplicons were selected for dual color fluorescence in situ hybridization analysis in approximately 90 high-grade serous carcinomas and 26 low-grade serous tumors, and a high level of DNA copy number gain (amplification) was found in CCNE1, Notch3, HBXAP/Rsf-1, AKT2, PIK3CA and chr12p13 occurring in 36.1%, 7.8%, 15.7%, 13.6%, 10.8% and 7.3% of high-grade serous carcinomas. In contrast, we did not observe high level of ERBB2 amplification in any of the samples. Low-grade tumors did not show DNA copy number gain in any of the loci, except in 2 (8%) of 24 low-grade tumors showing low copy number gain in the Notch3 locus. Taken together, our results provide the first comprehensive analysis of DNA copy number changes in highly pure ovarian serous carcinoma. These findings may have important biological and clinical implications.
Nakayama
Kentaro
K
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Nakayama
Naomi
N
Jinawath
Natini
N
Salani
Ritu
R
Kurman
Robert J
RJ
Shih
Ie-Ming
IeM
Wang
Tian-Li
TL
D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D019927:Cyclin E / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
C475820:CCNE1 protein, human; D019927:Cyclin E; C499374:NOTCH3 protein, human; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C452851:RSF1 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D015534:Trans-Activators; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt