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Chromosomal fragility in the cancer‐prone disease xeroderma pigmentosum preferentially involves bands relevant for cutaneous carcinogenesis
Author(s) -
Lanza Annalisa,
Lagomarsini Paola,
Casati Alessandra,
Ghetti Pierluigi,
Stefanini Miria
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971219)74:6<654::aid-ijc17>3.0.co;2-5
Subject(s) - xeroderma pigmentosum , carcinogenesis , chromosomal fragile site , cancer , carcinogen , biology , mutagen , genetics , skin cancer , pathology , cancer research , microbiology and biotechnology , medicine , chromosome , dna repair , dna , gene
Spontaneous and folate‐induced chromosomal fragility was analyzed in peripheral blood lymphocytes from 6 patients affected by the cancer‐prone disease xeroderma pigmentosum (XP), from the parents of 4 of the patients, and from 12 normal subjects. All XP patients were defective in nucleotide‐excision repair; 4 belonged to group C and 1 each to groups A and D. A tendency toward increased spontaneous chromosomal fragility was observed in the XP family members, and lesions indicating substantial chromosomal damage, which were not observed in any healthy donors, were frequently found. The spontaneous lesion sites in lymphocytes from homozygous and heterozygous carriers of XP defects appeared to be significantly associated with those observed in normal skin fibroblasts from the same subjects. These XP spontaneous fragility sites showed a statistically significant association with the rearrangement breakpoints reported in skin pre‐tumoral and tumoral lesions from normal and unrelated XP donors. Under conditions of folate deprivation, the chromosomal fragility level, the pattern and the frequency of expression of fragile sites in XP patients and in their parents were similar to normal. However, XP patients generally showed a higher susceptibility to breakage at sites described as mutagen and carcinogen targets. Int. J. Cancer 74:654–663, 1997.© 1997 Wiley‐Liss, Inc.