ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array-based comparative genomic hybridization.
Anaplastic thyroid carcinoma (ATC) is one of the most virulent of all human malignancies, with a mean survival time among patients of less than 1 year after diagnosis. To date, however, cytogenetic information on this disease has been very limited. During the course of a program to screen a panel of ATC cell lines for genomic copy-number aberrations using array-based comparative genomic hybridization, we identified a high-level amplification of the ITCH gene, which is mapped to 20q11.22 and belongs to the homologous to the E6-associated protein carboxylterminus ubiquitin ligase family. The expression of ITCH was increased in 4 of 14 ATC cell lines (28.6%), including 8305C in which there was a copy-number amplification of this gene, and six of seven primary cases (85.7%). Among the primary thyroid tumors, a considerable number of ITCH high expressers was found in ATC (40/45, 88.9%), papillary thyroid carcinoma (25/25, 100%), and papillary microcarcinoma (25/25, 100%). Furthermore, knockdown of ITCH by specific small interfering RNA significantly inhibited the growth of ITCH-overexpressing cells, whereas ectopic overexpression of ITCH promoted growth of ATC cell lines with relatively weak expression. These observations indicate ITCH to be the most likely target for 20q11.22 amplification and to play a crucial role in the progression of thyroid carcinoma.
Ishihara
Takaya
T
Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo, Japan.
Tsuda
Hitoshi
H
Hotta
Akiko
A
Kozaki
Ken-Ichi
K
Yoshida
Akira
A
Noh
Jaeduk Yoshimura
JY
Ito
Koichi
K
Imoto
Issei
I
Inazawa
Johji
J
D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002890:Chromosomes, Human, Pair 20; D055028:Comparative Genomic Hybridization; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D012097:Repressor Proteins; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases