Genome-wide analysis of genetic alterations in testicular primary seminoma using high resolution single nucleotide polymorphism arrays

• Published in: Genomics (San Diego, Calif.) Calif.), 2011-06, Vol.97 (6), p.341-349
• Main Authors: LeBron, Cynthia, Pal, Prodipto, Brait, Mariana, Dasgupta, Santanu, Guerrero-Preston, Rafael, Looijenga, Leendert H.J., Kowalski, Jeanne, Netto, George, Hoque, Mohammad O.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; chromosome 4; chromosome 9; Chromosome deletion; chromosomes; Chromosomes, Human - genetics; copy number; DNA Copy Number Variations; Fundamental and applied biological sciences. Psychology; Gene Amplification; Gene deletion; Genes, Neoplasm; Genes. Genome; Genetics of eukaryotes. Biological and molecular evolution; Genome-wide analysis; Genome-Wide Association Study; genomics; Germ cells; Gynecology. Andrology. Obstetrics; heterozygosity; homozygosity; Humans; Loss of Heterozygosity; Male; Male genital diseases; males; Malignancy; Medical sciences; Middle Aged; Molecular and cellular biology; Molecular genetics; neoplasms; Oligonucleotide Array Sequence Analysis; pathogenesis; Polymerase chain reaction; Polymorphism, Single Nucleotide; quantitative polymerase chain reaction; Seminoma; Seminoma - genetics; Sequence Analysis, DNA - methods; Sequence Deletion; Single-nucleotide polymorphism; SNP array; Testes; Testicular cancer; Testicular Neoplasms - genetics; Tumors
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2011.02.011

Testicular germ cell tumors (TGCT) represent the most common malignancy among young males. To our knowledge no comprehensive Copy Number Variation (CNVs) studies of TGCT using high-resolution Single Nucleotide Polymorphism (SNP) array have been performed. By a genome-wide analysis of CNV and loss of heterozygosity (LOH) in 25 primary seminomas, we confirmed several previously reported genomic alterations and discovered eight novel genomic alterations including amplifications and homozygous deletions. Moreover, a comparison of genomic alterations of early and late stage seminoma identified CNVs that correlate with progression, which included deletions in chromosomes 4q, 5p, 9q, 13q and 20p and amplifications in chromosomes 9q and 13q. We compared previously perform Affymetrix expression analysis in a subset of samples and found robust correlation between expression and genomic alterations. Furthermore, high correlations (40–75%) were observed between CNV by SNP analysis and quantitative PCR. Our findings may lead to better understanding of TGTC's pathogenesis.