Cytogenetic and molecular analysis of a family with three brothers afflicted with germ-cell cancer

• Published in: Clinical genetics 2004-01, Vol.65 (1), p.32-39
• Main Authors: Ottesen, AM, Rajpert-De Meyts, E, Holm, M, Andersen, I-LF, Vogt, PH, Lundsteen, C, Skakkebæk, NE
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Cell Differentiation; Chromosomes, Human, Pair 12 - genetics; cytogenetic investigation; endocrine disruptors; Environmental Exposure; familial testicular cancer; General aspects. Genetic counseling; Genetic Predisposition to Disease; germ-cell neoplasm; hereditary factors; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Life Style; Male; Medical genetics; Medical History Taking; Medical sciences; Neoplasms, Germ Cell and Embryonal - genetics; Neoplasms, Germ Cell and Embryonal - pathology; Nucleic Acid Hybridization; Pedigree; Siblings; Testicular Neoplasms - genetics; Testicular Neoplasms - pathology
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j..2004.00180.x

A thorough cytogenetic investigation and an analysis of detailed questionnaires were performed in a family with three brothers afflicted with germ‐cell tumors (GCTs), in an attempt to detect a congenital factor related either to a hereditary genetic background or an environmental/lifestyle influence. One brother had an intracranial tumor in the pineal region and the two others had testicular tumors. Peripheral blood was studied by traditional karyotyping, multicolor‐FISH, high‐resolution comparative genomic hybridization (HR‐CGH), and molecular analysis of selected loci on sex chromosomes (Yq11 region, TSPY, and the androgen receptor gene); however, no abnormalities were detected. The HR‐CGH analysis of microdissected histological components of the overt tumors and the adjacent carcinoma in situ demonstrated a pattern of genomic imbalances characteristic for sporadic GCTs, including gain of 12p. The questionnaire and interview revealed a history of different cancers in the extended family, and a possible in utero and/or infantile exposure of the three brothers with GCTs to compounds suspected of endocrine‐disrupting properties. Although no genetic aberration was detected in this family, we suspect the presence of a recessive hereditary factor pre‐disposing to cancer, which probably was manifested as GCTs in the three brothers because of an adverse effect of an environmental factor on the early germ‐cell differentiation.