A UNIQUE SPECTRUM OF P53 MUTATIONS IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA DISTINCT FROM THAT OF OTHER LYMPHOID MALIGNANCIES

The spectrum and pattern of p53 mutations detected in 42 cases of B-ce ll chronic lymphocytic leukemia (B-CLL) were analyzed, and several int eresting features were noted. Codon 209 in the p53 gene may be a new h ot-spot for p53 mutation in B-CLL disease. Four of the 42 (10%) report ed B-CLL p53 mutations occurred at codon 209 versus none in 214 cases of other lymphoid malignancies screened for p53 mutations (P = 0.0006) . Transversion mutations predominated at codon 273 rather than the tra nsition mutations that are known to occur at this CpG site. Four of si x (67%) B-CLL cases had transversions at codon 273 compared with two o f 17 (12%) of all other lymphoid tumors examined (P = 0.02). In additi on, over 65% of the p53 mutations detected in B-CLL showed a strand bi as for p53 mutations on the untranscribed DNA strand. This feature of DNA strand bias is notable in cancers of the lung, esophagus, and head and neck, which may result from high exposure to carcinogens. This sp ectrum of p53 mutations in B-CLL together with the high frequency of t ransversion mutations and DNA strand bias may implicate environmental carcinogens associated with p53 gene damage in some B-CLL patients. (C ) 1995 Wiley-Liss, Inc.