Candidate diagnostic markers and tumor suppressor genes for adrenocortical carcinoma by expression profile of genes on chromosome 11q13.
BACKGROUND
The most common genetic change observed in adrenocortical carcinoma is loss of heterozygozity on chromosome 11q13. As genes on this chromosome may be important in the pathogenesis of adrenocortical carcinoma, we compared their expression profile between benign and malignant adrenocortical tissue.


METHODS
We used the Affymetrix GeneChip (U133 plus 2.0) array in 54 adrenocortical tumors (11 carcinoma and 43 benign). Differential gene expression was defined as a twofold higher or lower gene expression level (p<0.05). Differentially expressed genes on microarray analysis were validated by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The area under the receiver operating characteristic (ROC) curve (AUC) was used to determined the diagnostic accuracy of the differently expressed genes for distinguishing benign from malignant tumors.


RESULTS
We found 25 of the 314 genes on chromosome 11q13 to be differentially expressed between adrenocortical carcinoma and benign adrenocortical tumor. All 25 were downregulated in adrenocortical carcinoma by 2-fold to 4.8-fold; 21 were validated to be differentially expressed by RT-PCR (Pearson's coefficient>0.5). Six genes (SERPING1, MRPL48, TM7SF2, DDB1, NDUSF8, PRDX5) validated by RT-PCR were significantly differentially expressed between benign and malignant adrenocortical tumors (p<0.05) with an overall accuracy of 89% for SERPING1, 91% for MRPL48, 87% for TM7SF2, 88% for DDB1, 91% for NDUFS8, and 89% for PRDX5. The AUC was 0.89 for the combination of SERPING1, MRPL48, TM7SF2, DDB1, and NDUFS8.


CONCLUSIONS
We have identified 25 genes located on chromosome 11q13 that are downregulated in adrenocortical carcinoma and may be candidate tumor suppressor genes. Six of these genes were good diagnostic markers for distinguishing adrenocortical carcinoma from adenoma.
Fernandez-Ranvier
Gustavo G
GG
Department of Surgery, University of California, San Francisco, School of Medicine, UCSF/Mt. Zion Medical Center, 1600 Divisadero Street, San Francisco, CA 94143-1674, USA.
Weng
Julie
J
Yeh
Ru-Fang
RF
Shibru
Daniel
D
Khafnashar
Elham
E
Chung
Ki-Wook
KW
Hwang
Jimmy
J
Duh
Quan Yang
QY
Clark
Orlo H
OH
Kebebew
Electron
E
D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018268:Adrenocortical Carcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve
D005819:Genetic Markers