Global expression analysis of cancer/testis genes in uterine cancers reveals a high incidence of BORIS expression.
OBJECTIVE
Cancer/testis (CT) genes predominantly expressed in the testis (germ cells) and generally not in other normal tissues are aberrantly expressed in human cancers. This highly restricted expression provides a unique opportunity to use these CT genes for diagnostics, immunotherapeutic, or other targeted therapies. The purpose of this study was to identify those CT genes with the greatest incidence of expression in uterine cancers.


METHODS
We queried the expression of known and putative CT gene transcripts (representing 79 gene loci) using whole genome gene expression arrays. Specifically, the global gene expressions of uterine cancers (n = 122) and normal uteri (n = 10) were determined using expression data from the Affymetrix HG-U133A and HG-U133B chips. Additionally, we also examined the brother of the regulator of imprinted sites (BORIS) transcript by reverse transcription-PCR and quantitative PCR because its transcript was not represented on the array.


RESULTS
Global microarray analysis detected many CT genes expressed in various uterine cancers; however, no individual CT gene was expressed in more than 25% of all cancers. The expression of the two most commonly expressed CT genes on the arrays, MAGEA9 (24 of 122 cancers and 0 of 10 normal tissues) and Down syndrome critical region 8 (DSCR8)/MMA1 (16 if 122 cancers and 0 of 10 normal tissues), was confirmed by reverse transcription-PCR methods, validating the array screening approach. In contrast to the relatively low incidence of expression of the other CT genes, BORIS expression was detected in 73 of 95 (77%) endometrial cancers and 24 of 31 (77%) uterine mixed mesodermal tumors.


CONCLUSIONS
These data provide the first extensive survey of multiple CT genes in uterine cancers. Importantly, we detected a high frequency of BORIS expression in uterine cancers, suggesting its potential as an immunologic or diagnostic target for these cancers. Given the high incidence of BORIS expression and its possible regulatory role, an examination of BORIS function in the etiology of these cancers is warranted.
Risinger
John Ian
JI
Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. risin.Jo1@memorialhealth.com
Chandramouli
Gadisetti V R
GV
Maxwell
G Larry
GL
Custer
Mary
M
Pack
Svetlana
S
Loukinov
Dmitri
D
Aprelikova
Olga
O
Litzi
Tracy
T
Schrump
David S
DS
Murphy
Susan K
SK
Berchuck
Andrew
A
Lobanenkov
Victor
V
Barrett
J Carl
JC
D000951:Antigens, Neoplasm / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013737:Testis / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism
D000951:Antigens, Neoplasm; C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; C453740:DSCR8 lncRNA, human; C520253:MAGEA9 protein, human; D009363:Neoplasm Proteins