BRIEF COMMUNICATION Monosomy and ring chromosome 13 in a thyroid nodular goiterddo we underestimate its relevance in benign thyroid lesions? Wolfgang Sendt a , Volkhard Rippe b , Inga Flor b , Norbert Drieschner b , J € orn Bullerdiek b, * a Department of General and Visceral Surgery of the St. Joseph Stift, Bremen, Germany; b Center for Human Genetics, University of Bremen, Bremen, Germany Classical cytogenetic examination of a thyroid nodular goiter revealed the existence of two different cytogenetically aberrant cell clones. They were characterized by monosomy 13 as the sole abnor- mality in one clone, and loss of one chromosome 13 and a ring chromosome that was found to consist of chromosome 13 material by fluorescence in situ hybridization in the other clone. We have concluded that during the course of karyotypic evolution, the instability of the ring chromosome has led to its loss and subsequent monosomy 13. In the literature, two cases of partial monosomy 13 have been reported in adenomatous goiters, suggesting that this abnormality characterizes a rare but distinct subgroup of benign thyroid lesions histologically presenting as adenomatous goiters. Possible target genes of these deletions are the retinoblastoma (RB1) gene locus and the MIR16-1/15A cluster. Based on similar changes in other tumors, it seems reasonable to also analyze a large number of adenomatous goiters for submicroscopic deletions of the long arm of chromosome 13. Keywords Thyroid, nodular goiter, chromosome 13, ring chromosome, cytogenetics ª 2012 Elsevier Inc. All rights reserved. Thyroid adenomas, and with a much lower frequency nodular goiters, can show clonal chromosome abnormalities. Struc- tural chromosomal rearrangements of either chromosomal band 19q13 or 2p21 and trisomy 7 are the most frequent recurrent alterations. Other rare karyotypic changes have occasionally been reported, including, for example, a deleted long arm of chromosome 13 in two cases of nodular goiters (1). Here, we describe a third case of a nodular goiter showing aberrations of chromosome 13. In this case, two cytogeneti- cally aberrant clones characterized by a ring chromosome 13 that led to partial monosomy 13 in one subline and a complete monosomy 13 in the other, dominant subline were noted. Materials and methods Cell culture and cytogenetics A tissue sample of a surgically removed nodular goiter of a 60-year-old female patient was used to set up cell cultures as described previously (1). From the primary culture, 16 metaphases were karyotyped by following routine proce- dures for chromosome analysis in classical cytogenetics. Fluorescence in situ hybridization Fluorescence in situ hybridization (FISH) was performed as described previously (2), with the exception of posthybridiza- tion, which was performed according to the manufacturer’s protocol (Abbott Molecular, Wiesbaden, Germany). The LSI D13S319 (13q14.3) SpectrumOrange and LSI 13q34 Spec- trumGreen (LAMP1; 13q34) (Abbott Molecular) probes were used in one hybridization mixture with a total volume of 10 mL containing 1 mL of each probe, 1 mL aqua bidest, and 7 mL hybridization buffer (Abbott Molecular). A total of 38 additional metaphases were analyzed. Results Of the 16 karyotyped metaphases, 11 showed monosomy 13 as the sole chromosome abnormality, and 5 had a ring chro- mosome (Figure 1) with absence of the second intact chro- mosome 13. The ring chromosome could not be further Received October 6, 2011; received in revised form January 19, 2012; accepted January 19, 2012. * Corresponding author. E-mail address: bullerd@uni-bremen.de 2210-7762/$ - see front matter ª 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergen.2012.01.010 Cancer Genetics 205 (2012) 128e130