Spontaneous abnormalities in normal fibroblasts from patients with Li-Fraumeni cancer syndrome : aneuploidy and immortalization

Families of patients with the Li-Fraumeni cancer syndrome have an inherited pattern of sarcomas and various other types of cancers that follow a dominant mode of transmission, an early age of onset, and exhibit multiple primary tumors. As soft tissue sarcomas (including fibrosarcomas) are frequently...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1990-12, Vol.50 (24), p.7979-7984
Main Authors: BISCHOFF, F. Z, YIM, S. O, PATHAK, S, GRANT, G, SICILIANO, M. J, GIOVANELLA, B. C, STRONG, L. C, TAINSKY, M. A
Format: Article
Language:English
Subjects:
Aneuploidy
Biological and medical sciences
Cell Adhesion
Cell Division
Cell Line
Fibroblasts - cytology
Fibroblasts - pathology
Humans
Isoenzymes - analysis
Karyotyping
Medical sciences
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Neoplastic Syndromes, Hereditary - genetics
Neoplastic Syndromes, Hereditary - pathology
Neoplastic Syndromes, Hereditary - therapy
Tumor Cells, Cultured - cytology
Tumors
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Summary:Families of patients with the Li-Fraumeni cancer syndrome have an inherited pattern of sarcomas and various other types of cancers that follow a dominant mode of transmission, an early age of onset, and exhibit multiple primary tumors. As soft tissue sarcomas (including fibrosarcomas) are frequently observed with this syndrome, the in vitro growth characteristics of fibroblasts derived from skin biopsies of Li-Fraumeni syndrome patients were studied. Control fibroblasts maintained a normal morphology and eventually senesced in culture. Fibroblasts from seven of eight affected individuals developed changes in morphology, anchorage-independent growth, and chromosomal abnormalities. In a fashion similar to that of fibroblasts from normal donors they underwent a growth crisis during which their growth was slow, but they continued to grow past the point at which control samples had stopped dividing (35 population doublings). Fibroblasts from Li-Fraumeni cancer patients escape senescence, growing well beyond 35 population doublings with growth rates similar to early-passage cells. Patient fibroblasts maintain the morphology of a transformed cell but remain nontumorigenic in nude mice. These observations of the behavior of fibroblasts from patients with the Li-Fraumeni syndrome may have predictive value for the determination of gene carriers within these families who are at high risk of cancer.
ISSN:0008-5472
1538-7445