Cytogenetic and molecular analysis of a family with three brothers afflicted with germ-cell cancer.
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.
Ottesen
A M
AM
Department of Growth & Reproduction, Julianne Marie Center, University Hospital of Copenhagen, Blegdamsveg, Denmark.
Rajpert-De Meyts
E
E
Holm
M
M
Andersen
I-L F
IL
Vogt
P H
PH
Lundsteen
C
C
Skakkebaek
N E
NE
D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D004781:Environmental Exposure; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008019:Life Style; D008297:Male; D008487:Medical History Taking; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D035781:Siblings; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology