title: Genomic copy number analysis of Chernobyl papillary thyroid carcinoma in the Ukrainian-American Cohort.
abstract: One of the major consequences of the 1986 Chernobyl reactor accident was a dramatic increase in papillary thyroid carcinoma (PTC) incidence, predominantly in patients exposed to the radioiodine fallout at young age. The present study is the first on genomic copy number alterations (CNAs) of PTCs of the Ukrainian-American cohort (UkrAm) generated by array comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering of CNA profiles revealed a significant enrichment of a subgroup of patients with female gender, long latency (>17 years) and negative lymph node status. Further, we identified single CNAs that were significantly associated with latency, gender, radiation dose and BRAF V600E mutation status. Multivariate analysis revealed no interactions but additive effects of parameters gender, latency and dose on CNAs. The previously identified radiation-associated gain of the chromosomal bands 7q11.22-11.23 was present in 29% of cases. Moreover, comparison of our radiation-associated PTC data set with the TCGA data set on sporadic PTCs revealed altered copy numbers of the tumor driver genes NF2 and CHEK2. Further, we integrated the CNA data with transcriptomic data that were available on a subset of the herein analyzed cohort and did not find statistically significant associations between the two molecular layers. However, applying hierarchical clustering on a 'BRAF-like/RAS-like' transcriptome signature split the cases into four groups, one of which containing all BRAF-positive cases validating the signature in an independent data set.
authors: Martin
authors: M
authors: Selmansberger
authors: Herbert
authors: H
authors: Braselmann
authors: Julia
authors: J
authors: Hess
authors: Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of the Ukraine, 254114 Kiev, Ukraine.
authors: Tetiana
authors: T
authors: Bogdanova
authors: Bundeswehr Institute of Radiobiology, 80937 Munich, Germany and.
authors: Michael
authors: M
authors: Abend
authors: Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of the Ukraine, 254114 Kiev, Ukraine.
authors: Mykola
authors: M
authors: Tronko
authors: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI , Bethesda, MD 20892, USA.
authors: Alina
authors: A
authors: Brenner
authors: Horst
authors: H
authors: Zitzelsberger
authors: Kristian
authors: K
authors: Unger
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D047852:Chernobyl Nuclear Accident; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D008297:Male; D020125:Mutation, Missense; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D011847:Radioactive Fallout / Q000009:adverse effects*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D014455:Ukraine / Q000208:ethnology; D014481:United States
chemical_list: D007457:Iodine Radioisotopes; D011847:Radioactive Fallout; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf