DNA Copy Number Aberrations in Thyroid Tumors Determined Using SNP Arrays
M Gandhi, MA Lyons-Weiler, UR Chandran, WA LaFramboise, YE Nikiforov. University of Pittsburgh, Pittsburgh, PA
Background: Changes in DNA copy number, such as deletions and amplifications, are common in cancer and frequently play an important role in tumor origination and progression. Single-nucleotide polymorphism (SNP) microarrays (SNP arrays), particularly those of high-density, allow effective detection of copy number changes in the entire genome. DNA copy number aberrations have not been systematically studied in thyroid cancer using high-density SNP arrays.
Design: We used Affymetrix Genome-Wide Human SNP Array 6.0 that contains 1.8 million genetic markers for the detection of copy number variation in 12 thyroid papillary carcinomas (PC) (including 6 classic papillary (PC,CL) and 6 follicular variants (PC,FV)), 6 follicular carcinomas (FC), and 5 follicular adenomas (FA). In addition, 9 matching normal thyroid tissues were used. For all samples, DNA was isolated from snap frozen tissue. Copy number estimates were calculated using Partek Genomics Suite (Partek, St. Louis, MO) with the averaged 9 normal samples as a baseline. All tumor samples were genotyped for BRAF mutation.
Results: On principle component analysis, FAs formed a separate cluster from malignant tumors, whereas PC,CL, PC,FV, and FC showed no particular grouping. Further analysis of PC revealed 16 regions of deletion and 24 regions of amplification frequently present in these tumors. Among those, deletions on 1p13.3 were found in 50% of PC,CL and 50% PC,FV, whereas all other deletions were more common in PC,FV than in PC,CL, including loci on 3p26.3, 3p26.1, 13q21 and 13q31 (all found in 67% of PC,FV vs 17% PC,CL), and locus on 3p24.1 (83% vs 0). Multiple deletions were found in one PC,CL tumor that carried BRAF mutation. Most common loci of amplifications were on chromosomes 7q11, 10q21, and 19p13. Multiple amplification events were found in 33% of PC,CL (both BRAF positive tumors) and 83% of PC,FV.
Conclusions: Our results show that in thyroid tumors, DNA copy number aberrations, including both deletions and amplifications, are more common in follicular variant papillary carcinomas than in classic papillary carcinomas. The most dramatic differences between the two tumor subtypes were observed in deletion on 3p24.1 and in amplification of 7q11.23 and 10q21.3. Among classic papillary carcinomas, multiple DNA copy number aberrations were more common in tumors with BRAF mutation, consistent with the known correlation between this mutation and more aggressive tumor behavior.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 77, Tuesday Afternoon