Hypersensitivity to G2 chromatid radiation damage in familial dysplastic naevus syndrome

Skin fibroblasts from 25 members of nine kindreds with familial dysplastic naevus syndrome (DNS), 12 apparently normal spouses, and 11 additional unrelated normal individuals were tested for G2 cell-cycle phase sensitivity to ionising radiation. The cells from individuals with DNS or hereditary cutaneous malignant melanoma with DNS (HCMM/DNS) had significantly more chromatid breaks and gaps when entering metaphase 0.5-1.5 h after G2 phase X-irradiation (1 Gy) than those from unaffected controls. In two cases, the test results positively identified individuals before the clinical diagnosis of DNS. A clinically normal obligate carrier of the HCMM/DNS gene showed the enhanced G2 radiosensitivity. Moreover, in a test on 1 proband, the sensitivity was apparent in peripheral blood lymphoblasts. Enhanced G2 chromatid radiosensitivity may be a marker of genetic susceptibility to HCMM/DNS.