Liability to chromosome damage in lymphocytes of "cancer family" subjects: a study of spontaneous and induced chromosomal fragility.
Spontaneous chromosomal fragility was detected in seven tumor patients and one healthy member from two families with a high recurrence of cancer. Major chromosome lesions, such as terminal deletions and rearranged chromosomes, were found at levels significantly higher than those reported for control individuals. The prevalence of these aberrations in comparison to minor ones (chromosome gaps and chromatid breaks) in this group of patients seems to indicate that the fragility observed is the end-point of a process of chromosomal instability, which may have already been brought to expression. Study of other parameters of genetic instability in the most unstable karyotypes showed that the chromosome damage observed was neither paralleled by abnormal SCE frequency nor sustained by defective DNA repair mechanisms or expression of inherited or constitutional fragile sites. As all the subjects investigated here had previously been shown to display intraindividual variations in the C-banded region of chromosome 1, it is possible that spontaneous fragility and acquired C-heterochromatin polymorphism may be markers that, combined with chromosomal instability, create genetic predisposition to cancer.
Dipartimento di Biologia e Genetica per le Scienze Mediche, Milan, Italy.
L
L
Larizza
L
L
Doneda
M
M
Stefanini
G
G
Francone
V
V
Gualandri
A
A
Fuhrman Conti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D005153:Facial Neoplasms / Q000235:genetics; D005260:Female; D005833:Genital Neoplasms, Female / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D008545:Melanoma / Q000235:genetics; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics*