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Association between Large-scale Genomic Homozygosity without Chromosomal Loss and Nonseminomatous Germ Cell Tumor Development

Departments of ¹ Medical Oncology and ² Histopathology, Barts and London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom; and ³ Molecular Cytogenetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom

Requests for reprints: Yong-Jie Lu, Department of Medical Oncology, Barts and London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London, United Kingdom EC1M 6BQ. Phone: 44-20-7882-6140; Fax: 44-20-7882-6004; E-mail: yong.lu{at}cancer.org.uk.

The genotype of a tumor determines its biology and clinical behavior. The genetic alterations associated with the unique embryonal morphology of nonseminomatous subtypes of testicular germ cell tumors remain to be established. Using single nucleotide polymorphism microarray analysis, we found in all of the 15 nonseminomas analyzed, large-scale chromosomal homozygosities, most of which were not associated with relative chromosome loss. This unusual genotype, distinguishing nonseminoma from seminomas and other human tumors, may be associated with the special embryonal development morphologic transition of this malignancy. Based on these genetic data, we hypothesized a new potential origin of nonseminomas through sperm fusion. Nonrandom involvement of certain chromosomes also suggests that genes on these chromosome regions may play an important role in nonseminoma development.

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