Copy Number Alteration and Uniparental Disomy Analysis Categorizes Japanese Papillary Thyroid Carcinomas into Distinct Groups

<div><p>The aim of the present study was to investigate chromosomal aberrations in sporadic Japanese papillary thyroid carcinomas (PTCs), concomitant with the analysis of oncogene mutational status. Twenty-five PTCs (11 with <em>BRAF^V600E</em>, 4 with <em>RET/PTC1</em>, and 10 without mutation in <em>HRAS</em>, <em>KRAS</em>, <em>NRAS</em>, <em>BRAF</em>, <em>RET/PTC1</em>, or <em>RET/PTC3</em>) were analyzed using Genome-Wide Human SNP Array 6.0 which allows us to detect copy number alteration (CNA) and uniparental disomy (UPD), also referred to as copy neutral loss of heterozygosity, in a single experiment. The Japanese PTCs showed relatively stable karyotypes. Seven cases (28%) showed CNA(s), and 6 (24%) showed UPD(s). Interestingly, CNA and UPD were rarely overlapped in the same tumor; the only one advanced case showed both CNA and UPD with a highly complex karyotype. Thirteen (52%) showed neither CNA nor UPD. Regarding CNA, deletions tended to be more frequent than amplifications. The most frequent and recurrent region was the deletion in chromosome 22; however, it was found in only 4 cases (16%). The degree of genomic instability did not depend on the oncogene status. However, in oncogene-positive cases (<em>BRAF^V600E</em> and <em>RET/PTC1</em>), tumors with CNA/UPD were less frequent (5/15, 33%), whereas tumors with CNA/UPD were more frequent in oncogene-negative cases (7/10, 70%), suggesting that chromosomal aberrations may play a role in the development of PTC, especially in oncogene-negative tumors. These data suggest that Japanese PTCs may be classified into three distinct groups: CNA⁺, UPD⁺, and no chromosomal aberrations. <em>BRAF^V600E</em> mutational status did not correlate with any parameters of chromosomal defects.</p>