Laboratory Investigation
United States and Canadian Academy of Pathology The United States and Canadian Academy of Pathology
LWW Lippincott Williams and Wilkins
publishes Laboratory Investigation
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  Frequent Chromosomal DNA Unbalance in Thyroid Oncocytic (Hürthle Cell) Neoplasms Detected by Comparative Genomic Hybridization
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  Giovanni Tallini, Aileen Hsueh, Steven Liu, Ginesa Garcia-Rostan, Michael R. Speicher, and David C. Ward
   
  Department of Pathology (GT, GG-R) and Department of Genetics (AH, SL, MRS, DCW), Yale University School of Medicine, New Haven, Connecticut
   
  Thyroid oncocytic (Hürthle cell) neoplasms represent a distinct subset of follicular thyroid tumors characterized by abnormal accumulation of mitochondria, whose chromosomal abnormalities have never been systematically analyzed. We have used comparative genomic hybridization to investigate chromosomal DNA alterations in 11 thyroid oncocytic tumors (7 adenomas and 4 carcinomas). Unbalanced chromosomal DNA profiles were detected in 6 of 7 adenomas and 3 of 4 carcinomas, numerical chromosomal aberrations being the dominant feature. Comparative genomic hybridization findings are compatible with two separate groups of tumors with karyotypic abnormalities, one characterized by multiple chromosomal gains with polysomy of chromosomes 5 and 7, the other by loss of chromosome 2. Pathologic and clinical features were similar in the two groups with no difference observed between adenomas and carcinomas. Activating H-, K-, or N-Ras mutations are commonly detected in follicular adenomas and carcinomas of the thyroid gland. However, Ras mutational analysis demonstrated that only one of the tumors in this series, an oncocytic carcinoma with a balanced karyotype, had activating Ras mutations (at codon 13 of K-Ras). The lack of Ras mutations in the 9 oncocytic neoplasms exhibiting chromosomal aneuploidy indicates that numerical chromosomal abnormalities are independent of activating Ras mutations in oncocytic tumors. (Lab Invest, 79:547-555).