A unique spectrum of p53 mutations in B‐cell chronic lymphocytic leukemia distinct from that of other lymphoid malignancies

Abstract

The spectrum and pattern of p53 mutations detected in 42 cases of B-cell chronic lymphocytic leukemia (B-CLL) were analyzed, and several interesting features were noted. Codon 209 in the p53 gene may be a new hot-spot for p53 mutation in B-CLL disease. Four of the 42 (10%) reported 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 transition mutations that are known to occur at this CpG site. Four of six (67%) B-CLL cases had transversions at codon 273 compared with two of 17 (12%) of all other lymphoid tumors examined (P = 0.02). In addition, over 65% of the p53 mutations detected in B-CLL showed a strand bias 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 spectrum of p53 mutations in B-CLL together with the high frequency of transversion mutations and DNA strand bias may implicate environmental carcinogens associated with p53 gene damage in some B-CLL patients.

TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations

“…13 The study found a high incidence of codon 209 mutations (10%) and a high incidence of transversions in codon 273. This 'unusual' profile at CpG sites was suggested to implicate an exogenous carcinogen.…”

“…The studies that have been reported included 13À46 patients with mutations and therefore these results are subject to bias. [11][12][13][14] In addition, detailed analysis of clinical or genetic characteristics was not possible and is also not possible from an analysis of the databases.…”

TP53 Mutation Analysis in Clinical Practice: Lessons From Chronic Lymphocytic Leukemia

“…The spectrum of TP53 mutations identified in CLL patients is similar to other cancers, but some disease‐specific characteristics were identified [Newcomb et al., ; Zenz et al., ]. A large international collaborative study analyzing 268 mutations from four independent cohorts [Zenz et al, ] showed a lower proportion of transitions at CpG sites compared with other cancers (e.g., colon cancer), which was not attributed to the decreased number of all transitions.…”

Anticipation in familial chronic lymphocytic leukaemia

“…7 Mutations in TP53 and lesions indicating defective responses in DNA repair have been reported. 8,9 A number of studies have examined the cancer risks associated with a family history of lymphoproliferative disorders, including CLL (Table 1). They show an elevated risk of lymphoproliferative disorders in relatives.…”