P53 MUTATIONS IN HUMAN LYMPHOID MALIGNANCIES - ASSOCIATION WITH BURKITT-LYMPHOMA AND CHRONIC LYMPHOCYTIC-LEUKEMIA
P53 MUTATIONS IN HUMAN LYMPHOID MALIGNANCIES - ASSOCIATION WITH BURKITT-LYMPHOMA AND CHRONIC LYMPHOCYTIC-LEUKEMIA
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DOI：
10.1073/pnas.88.12.5413
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
DALLAFAVERA, R
中科院分区：
文献类型：
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作者：
GAIDANO, G;BALLERINI, P;DALLAFAVERA, R
我们研究了人类B细胞和T细胞淋巴系统恶性肿瘤，包括急性淋巴细胞性白血病、非霍奇金淋巴瘤的主要亚型和慢性淋巴细胞性白血病中p53突变的频率。采用单链构象多态分析和直接测序的方法，对197例原发肿瘤和27例细胞株的P53基因外显子5-9进行了研究。发现的突变与(I)Burkitt淋巴瘤(9/27例活检；17/27个细胞系)及其白血病对应的L3型B细胞急性淋巴细胞性白血病(5/9)有关，这两种白血病都携带激活的c-myc癌基因；(Ii)B细胞慢性淋巴细胞性白血病(6/40)，特别是其进展期称为里希特变(3/7)。在其他类型的非霍奇金淋巴瘤或急性淋巴细胞白血病中未发现任何显著频率的突变。在许多情况下，只有突变的等位基因可被检测到，这意味着正常等位基因的丢失。这些结果提示：(1)同一组织来源的不同肿瘤亚型的P53突变频率存在显著差异；(2)P53可能在B细胞慢性淋巴细胞白血病的肿瘤进展中起作用；(3)P53丢失/失活和c-myc癌基因激活可能在Burkitt淋巴瘤及其白血病L3型急性淋巴细胞白血病的发病机制中起重要作用。
We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direct sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsies; 17/27 cell lines) and its leukemic counterpart L3-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia.