A study of adrenocortical tumors in children and adolescents by a comparative genomic hybridization technique Elvis Cueva Mateo a, *, Cecı ´lia F. Lorea a , Antonio A. Duarte a , Daniel Moreno b , L. Neder c , Silvio Tucci Junior d , Carlos A. Scrileli a , Luiz G. Tone a a Department of Pediatrics, Division of Pediatric Oncology, School of Medicine of Ribeir ~ ao Preto, University of S~ ao Paulo, S~ ao Paulo, Brazil; b Department of Genetics, School of Medicine of Ribeir ~ ao Preto, University of S~ ao Paulo, S~ ao Paulo, Brazil; c Department of Pathology, School of Medicine of Ribeir ~ ao Preto, University of S~ ao Paulo, S~ ao Paulo, Brazil; d Department of Anatomy and Surgery, School of Medicine of Ribeir ~ ao Preto, University of S~ ao Paulo, S~ ao Paulo, Brazil Adrenocortical tumors (ACT) are rare neoplasms of the adrenal glands accounting for 0.2% of all pediatric cancers. However, the incidence of ACT in South Brazilian children is 10 to 15 times greater than the worldwide incidence. Comparative genomic hybridization studies have revealed the presence of a high degree of chromosomal instability in ACT. We evaluated 16 ACT, 8 of them carcinomas and 8 adenomas. The presence of changes in DNA copy numbers was deter- mined by comparative genomic hybridization, and the findings were validated by real-time poly- merase chain reaction on the basis of IGF-II gene expression. The adenomas showed a mean of 19.7 imbalances per case, with the most frequent gain and loss being 4p15.1ep15.3 and 20p11.2ep13.2, respectively. The carcinomas presented with a mean of 35.5 imbalances per case, with the more frequent gain being 2q14.1eq24.3 and the more frequent losses being 3q21eq26.2, 20q12eqter, and 22q11.2eq13.3. The most frequent imbalances in both adenomas and carcinomas were gains of 1p21ep31.2, 2p12ep21 and loss of 20p11.2ep12. The expression of IGF-II mRNA (11p15.5) was higher in samples that presented with a gain of this region. It has been established that great genomic instability exists in pediatric ACT. Keywords Adrenocortical tumors (ACT), DNA copy number alterations (CNAs), comparative genomic hybridization (CGH) ª 2011 Elsevier Inc. All rights reserved. Adrenocortical tumors (ACT) are rare neoplasms, but their incidence in South Brazil is high, being 10e15 times higher than the incidence in the rest of the world (1). The histological differentiation between the two subtypes, adenomas and carcinomas, is difficult, however it has been shown that 10e20% of the pediatric cases are adenomas (2). Some characteristics have been associated with malignant clinical behavior such as age >3 years, tumor volume >200 cm 3 , and abnormal hormone levels, which persist after surgery (3,4). Tumorigenesis is a process consisting of multiple steps that determine a progressive transformation of normal cells to cancerous cells (5). Clonal studies have indicated that adrenocortical carcinomas are monoclonal tumors, whereas most adenomas are polyclonal (6), suggesting a possible progression from adenomas to carcinomas. ACT frequency is higher in patients with Beckwith-Wiedmann syndrome linked to the 11p15.5 region, which leads to overexpression of the insulin II growth factor gene (IGF-II ) (7), and in patients with Li-Fraumeni syndrome associated with inacti- vating mutations in the tumor suppressor gene TP53 in 17p13. The McCune-Albright and Carney syndromes and multiple endocrine neoplasm type I are also associated with the development of these tumors (8). Several molecules are important for the development of the adrenal glands. In particular, two transcription factors, steroidogenic factor 1(SF-1) and an encrypted factor for a critical region of the X chromosome associated with sex reversal and with congenital adrenal hypoplasia (DAX-1), are essential for adrenal development and differentiation (9). The fetal cortex occupies 85% of the adrenal cortex during embryonic Received May 12, 2010; received in revised form February 18, 2011; accepted February 22, 2011. * Corresponding author. E-mail address: ecuevamateo@yahoo.es 2210-7762/$ - see front matter ª 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergen.2011.02.006 Cancer Genetics 204 (2011) 298e308