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Chromosomal instability in fibroblasts and mesenchymal tumors from 2 sibs with Rothmund‐Thomson syndrome
Author(s) -
Miozzo Monica,
Castorina Pierangela,
Riva Paola,
Dalprà Leda,
Fuhrman Conti Anna Maria,
Volpi Ludovica,
Hoe Tuck S.,
Khoo Alan,
Wiegant Joop,
Rosenberg Carla,
Larizza Lidia
Publication year - 1998
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(19980812)77:4<504::aid-ijc5>3.0.co;2-y
Subject(s) - chromosome instability , biology , chromosome , karyotype , aneuploidy , trisomy , cytogenetics , genome instability , fibroblast , genodermatosis , microbiology and biotechnology , genetics , pathology , cancer research , gene , medicine , cell culture , dna , dna damage
Abstract Rothmund‐Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis associated with increased risk of mesenchymal tumors. The putative gene has been provisionally assigned to chromosome 8. Using a cytogenetic‐molecular approach, we studied lymphocytes, fibroblasts, osteosarcoma (OS) and malignant fibrous histiocytoma (MFH) from 2 affected fraternal twins, looking for constitutive markers of chromosome instability and tumor chromosomal changes which might reflect the common genetic background. The rate of spontaneous chromosome aberrations was not increased in lymphocytes. Conversely, karyotyping of primary fibroblasts from one sib evidenced chromosome breaks and both numerical and structural chromosome changes in 24% and 17% of the metaphases respectively. FISH of a 8q21.3 cosmid allowed us to detect trisomy of the target region on 7% of fibroblast nuclei from both sibs, 47% and 12% of OS and MFH cells. Pronounced chromosomal instability and clonal rearrangements leading to different chromosome‐8 derivatives were detected in both tumors. CGH experiments showed multiple gains/losses, among which del(6q), also revealed by cytogenetics, and 7p gain were common, whereas 8q amplification was present only in OS. Chromosomal instability, observed in fibroblasts from the RTS patients studied, accounts for the increased risk of mesenchymal tumors in these patients. Int. J. Cancer 77:504–510, 1998. © 1998 Wiley‐Liss, Inc.