Soft tissue sarcoma metastasis from clonal expansion of p53 mutated tumor cells.
Although soft tissue sarcoma has a high incidence of p53 mutations, it is not clear if such alterations facilitate tumor growth and metastasis. In this study, fresh autologous normal lymphocytes, normal muscle, primary and metastatic sarcoma tissues from a single synovial sarcoma patient were examined for p53-related alterations that potentially associated with sarcoma tumor development and metastasis. Normal tissues contain two wild-type p53 alleles. Primary sarcoma had one chromosome 17p p53 allelic deletion without apparent p53 mutation in the other allele. However, metastatic tumor had deletion of one p53 allele with an exon 5 codon 135 missense mutation in the other allele. This p53 gene point mutation in the metastasis was associated with the production of mutated p53 protein. A small clone of cells harboring the identical p53 gene point mutation was identified in the primary tumor using mutant allele specific PCR amplification, albeit at levels much less than in the metastatic sarcoma. This single patient example indicate that soft tissue sarcoma metastasis can develop from clonal expansion of primary tumor cells bearing p53 mutations.
Pollock
R E
RE
The University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, Houston 77030, USA.
Lang
A
A
Luo
J
J
El-Naggar
A K
AK
Yu
D
D
D001483:Base Sequence; D017931:DNA Primers; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D017931:DNA Primers