IngentaConnect Whole-genome profiling of chromosomal aberrations in hepatoblasto...

Authors: Suzuki, Makoto; Kato, Motohiro¹; Yuyan, Chen¹; Takita, Junko²; Sanada, Masashi³; Nannya, Yasuhito³; Yamamoto, Go³; Takahashi, Atsushi⁴; Ikeda, Hitoshi⁵; Kuwano, Hiroyuki⁴; Ogawa, Seishi; Hayashi, Yasuhide

Source: Cancer Science, Volume 99, Number 3, March 2008 , pp. 564-570(7)

Publisher: Blackwell Publishing

Abstract:

To identify the genomic profile and elucidate the pathogenesis of hepatoblastoma (HBL), the most common pediatric hepatic tumor, we performed high-density genome-wide single-nucleotide polymorphism (SNP) microarray analyses of 17 HBL samples. The copy number analyzer for GeneChip® (CNAG) and allele-specific copy number analysis using anonymous references (AsCNAR) algorithms enabled simple but sensitive inference of allelic composition without using paired normal DNA. Chromosomal aberrations were observed in 15 cases (88%). Gains in chromosomes 1q, 2 (or 2q), 8, 17q, and 20 and losses in chromosomes 4q and 11q were frequently identified. High-grade amplifications were detected at 7q34, 14q11.2, and 11q22.2. Several types of deletions, except homozygous deletion, were identified. Most importantly, copy-neutral loss of heterozygosity (uniparental disomy [UPD]) at 11p15 was detected in four of the 17 HBL samples. Insulin-like growth factor II (IGF2) and H19 genes were located within this region. The methylated status of this region indicated the paternal origin of the UPD. The expression patterns of IGF2 and H19 were opposite between genes with and without the UPD. This difference in the expression patterns might influence the clinical features of HBL. (Cancer Sci 2008; 99: 564-570)

Document Type: Research article

DOI: 10.1111/j.1349-7006.2007.00710.x

Affiliations: 1: Department of Pediatrics, 2: Department of Cell Therapy and Transplantation Medicine, 3: Department of Hematology and Oncology, and 4: Department of General Surgical Science, Graduate School of Medicine, Gunma University Graduate School, 3-39-15 Showa, Maebashi, Gunma 371-8511; 5: Department of Pediatric Surgery, Koshigaya Hospital, Dokkyo Medical School, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555;

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Whole-genome profiling of chromosomal aberrations in hepatoblastoma using high-density single-nucleotide polymorphism genotyping microarrays