Candidate Diagnostic Markers and Tumor Suppressor Genes for Adrenocortical Carcinoma by Expression Profile of Genes on Chromosome 11q13
- 186 Downloads
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.
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.
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.
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.
This work was supported in part by grants from the University of California San Francisco (UCSF) Comprehensive Cancer Center, the Mount Zion Health Fund, and the American Cancer Society.
The authors thank Dr. Christopher Barker of the UCSF Genomic Core for helpful technical assistance, and Pamela Derish, for helping to edit this manuscript.
- 3.Fehaily MA, Duh QY (2003) Adrenocortical carcinoma. In Clark OH, Duh QY, Perrier N et al (eds) Endocrine Tumors: American Cancer Society, Atlas of Clinical Oncology. BC Decker, Hamilton, Ontario, pp 123–130Google Scholar
- 5.Houdelette P, Chagnon A, Dumotier J et al (1989) Malignant adrenocortical tumor as a part of Wermer’s syndrome. Apropos of a case. J Chir (Paris) 126:385–387Google Scholar