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Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high‐level amplifications
Author(s) -
Dohna Martha,
Reincke Martin,
Mincheva Antoaneta,
Allolio Bruno,
SolinasToldo Sabina,
Lichter Peter
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(200006)28:2<145::aid-gcc3>3.0.co;2-7
Subject(s) - comparative genomic hybridization , adrenocortical carcinoma , biology , chromosome , cytogenetics , carcinogenesis , metastasis , cancer research , pathology , karyotype , carcinoma , tumor progression , adrenocortical adenoma , chromosomal region , gene duplication , genetics , cancer , adenoma , medicine , gene , endocrinology
Distinction of adrenocortical carcinoma from benign adrenocortical lesions by standard criteria is often difficult. In order to search for additional diagnostic parameters, a series of 25 adrenocortical tumors, 8 adenomas, 14 primary carcinomas, 1 metastasis, and the 2 adrenocortical carcinoma cell lines SW13 and NCI‐H295 were analyzed by the approach of comparative genomic hybridization (CGH). Except for the two smallest adenomas, all tumors showed chromosomal imbalances with a high incidence of chromosomal gains, most frequently involving chromosomes or chromosome arms 5, 7, 8, 9q, 11q, 12q, 14q, 16, 17q, 19, 20, and 22q. The only significant loss of material concerned the distal part of 9p. Furthermore, 21 high‐level amplifications were identified in 15 different regions of the genome. The consensus regions of recurrent gains and the focal high‐level amplifications allowed identification of a series of chromosomal subregions containing candidate proto‐oncogenes of potential pathogenic function in adrenocortical tumors: 1p34.3–pter, 1q22–q25, 3p24–pter, 3q29, 7p11.2–p14, 9q34, 11q12–11q13, 12q13, 12q24.3, 13q34, 14q11.2–q12, 14q32, 16p, 17q24–q25, 19p13.3, 19q13.4, and 22q11.2–q12. A subset of the CGH data was independently confirmed by interphase cytogenetics. Interestingly, the adenomas larger than 4 cm contained gained material of regions also overrepresented in carcinomas. In addition, several chromosomal gains, in particular the high‐level amplifications, were exclusive for the malignant status of the tumors. These data indicate that the larger adrenal lesions need to be carefully considered in the diagnosis of adrenocortical tumors, and that genetic aberrations might provide useful markers for a better diagnostic differentiation. Genes Chromosomes Cancer 28:145–152, 2000. © 2000 Wiley‐Liss, Inc.