title: Copy number alteration and uniparental disomy analysis categorizes Japanese papillary thyroid carcinomas into distinct groups.
abstract: 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 BRAF(V600E), 4 with RET/PTC1, and 10 without mutation in HRAS, KRAS, NRAS, BRAF, RET/PTC1, or RET/PTC3) 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 (BRAF(V600E) and RET/PTC1), 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. BRAF(V600E) mutational status did not correlate with any parameters of chromosomal defects.
authors.affiliation: Department of Radiation Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsuse
authors.forename: Kensaku
authors.initials: K
authors.lastname: Sasaki
authors.forename: Eijun
authors.initials: E
authors.lastname: Nishihara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Minami
authors.forename: Chisa
authors.initials: C
authors.lastname: Hayashida
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saenko
authors.forename: Koh-ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D015894:Genome, Human / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D024182:Uniparental Disomy / Q000235:genetics*; D055815:Young Adult