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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 |
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Department
of Pathology (GT, GG-R) and Department of Genetics (AH, SL, MRS, DCW), Yale
University School of Medicine, New Haven, Connecticut |
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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).
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