SINGLE SOMATIC RAS GENE POINT MUTATION IN SOFT-TISSUE MALIGNANT FIBROUS HISTIOCYTOMAS

The frequency of ras gene mutations in human soft tissue malignant fib rous histiocytomas within and around the hot spot codons (12, 13, and 61) of all ras genes, (N-ras-1, K-ras-2, and N-ras) was studied by nes ted polymerase chain reaction and direct DNA sequencing from archival formalin-fixed, paraffin-embedded tissue, Light microscopy and immunoh istochemistry served to define malignant fibrous histiocytoma, All of the four differentiation subtypes (storiform-pleomorphic, inflammatory , myxoid, and giant cell) were investigated. Nine of thirty-two malign ant fibrous histiocytomas (28%) contained ras gene point mutations. Th e highest incidence was found in the myxoid subtype (four of nine), H- ras-1 gene codon 12.2 was the only codon affected and contained in all mutated cases a GGC --> GTC exchange, Seven of the nine mutations wer e homozygous and probably affected more than 80% of the tumor DNA. The flanking regions of all hotspot codons did not contain any point muta tion, The presence of a single and often homozygous point mutation of the H-ras-1 gene, especially in myxoid malignant fibrous histiocytoma could serve as a basis for further genomic discrimination of myxoid sa rcomas.