Cytogenetic instability in young patients with multiple primary cancers

Patients younger than 45 years with multiple cancers and a family history of cancer were identified and examined for cytogenetic instability. The cohort included 50 individuals: 19 patients suffering from at least 2 independent cancers, 11 healthy control individuals, a positive control group of 5 highly radiosensitive patients (>grade 3, RTOG), and a tumor control group of 15 patients with a single tumor. Peripheral blood lymphocytes were irradiated in vitro (0.7 Gy, 2.0 Gy). Metaphase chromosomes 1, 2, and 4 were labeled by means of 3-color fluorescence in situ hybridization. Chromosomal aberrations (breaks per metaphase [B/M], complex chromosomal rearrangements [CCR/M]) were analyzed. Very high levels of chromosomal aberrations were detected in a “core group” of 5 patients. These patients displayed much higher rates of B/M and CCR/M than controls. Ten patients had moderately elevated chromosomal aberrations and 4 patients were indistinguishable from controls. We conclude that a significant proportion of young patients with multiple tumors and a family background of cancer display cytogenetic instability.