Putative gene loci associated with carcinogenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH.
OBJECTIVE
This study aimed to estimate the gene loci associated with carcinogenesis of endocervical adenocarcinoma of uterus (EA) and metastasis. Study design Sixteen patients with EA were studied; 6 had nodal metastasis. DNA was extracted from EAs, and subjected to both conventional comparative genomic hybridization (CGH) and array-based CGH. Copy number abnormalities were compared between cases with and without nodal metastasis.


RESULTS
In all EAs, high frequencies of copy number losses were detected in genes LRP1B (on 2q21.2), DAB2 (5p13), and DCC (18q21.3), as well as regions 3p, 16q, and 22q, and copy number amplifications in genes NRAS (1p13.2), TOP2A (17q21-q22), NCOA3(AIB1) (20q12), and ARSA (22q tel). Nodal metastasis was associated with high frequencies of copy number loss in genes PGRMC2 and LAMA3 and amplification in CDK6 and NCOA3(AIB1).


CONCLUSIONS
This is the first report of gene copy number alterations spanning the whole genome in EA. These altered genes are speculated to be associated with EAs as a tumor suppressor and/or oncogene.
Hirai
Yasuo
Y
Department of Gynecology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, 1-37-1 Kami-Ikebukuro, Toshimaku, Tokyo 170-8455, Japan. yhirai@jfcr.or.jp
Utsugi
Kuniko
K
Takeshima
Nobuhiro
N
Kawamata
Yasutaka
Y
Furuta
Reiko
R
Kitagawa
Tomoyuki
T
Kawaguchi
Tokuichi
T
Hasumi
Katsuhiko
K
Noda
Tetsuo
T
Noda
Shirahama Tetsuo
ST
D000123:Acetyltransferases; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D018628:Gene Dosage; D051548:Histone Acetyltransferases; D006801:Humans; D007797:Laminin / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011973:Receptors, LDL / Q000235:genetics*; D011980:Receptors, Progesterone; D015534:Trans-Activators / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C434476:LRP1B protein, human; D007797:Laminin; D008565:Membrane Proteins; D015513:Oncogene Proteins; C115297:PGRMC2 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D011973:Receptors, LDL; D011980:Receptors, Progesterone; D015534:Trans-Activators; C095567:laminin alpha 3; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human