N-RAS GENES ARE NOT MUTATED IN HODGKIN AND REED-STERNBERG CELLS - RESULTS FROM SINGLE-CELL POLYMERASE CHAIN-REACTION EXAMINATIONS

Ras mutations play an important role in many human tumors. They usuall y occur at only three codons (12, 13 and 61) of the three ras gene fam ily members and lead to altered proteins resulting in a constitutively activated downstream signal cascade. We have examined the N-ras gene status in Hodgkin's disease (HD). Little is known about the pathogenet ic events leading to the malignant phenotype in HD. Since Hodgkin and Reed-Sternberg (H and RS) cells comprise only a minority of the cellul ar infiltrate in HD-lymph nodes, molecular studies concerning the stat us of oncogenes have been difficult to perform and have yielded confli cting results. We have established a single cell PCR assay for N-ras a nalysis and have examined H and RS cells from 12 cases of HD by PCR am plification and direct sequencing. None of the single H and RS cells e xamined carried N-ras mutations at either codons 12/13 or 61. Therefor e, N-ras mutations are not involved in the pathogenesis of HD.